記述言語：英語   掲載種別：研究論文（学術雑誌）  

Urolithin A is a major metabolite produced by rats and humans after consumption of pomegranate juice or pure ellagitannin geraniin. In this study, we investigated the anti-inflammatory effect of urolithin A on carrageenan-induced paw edema in mice. The volume of paw edema was reduced at 1h after oral administration of urolithin A. In addition, plasma in treated mice exhibited significant oxygen radical antioxidant capacity (ORAC) scores with high plasma levels of the unconjugated form at 1h after oral administration of urolithin A. These results indicate strong associations among plasma urolithin A levels, the plasma ORAC scores, and anti-inflammatory effects and may help explain a mechanism by which ellagitannins confer protection against inflammatory diseases.

DOI： 10.1016/j.bmcl.2011.07.086

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Peroxisome proliferator-activated receptor γ (PPARγ) forms a heterodimeric DNA-binding complex with retinoid X receptors (RXRs). It has been reported that the effect of the PPAR agonist is reduced in hepatocyte RXR-deficient mice. Therefore, it is suggested that the endogenous RXR ligand is involved in the PPARγ agonist-induced anti-inflammatory effect. However, the participation of the RXR ligand in the PPARγ-induced anti-inflammatory effect is unknown. Here, we investigated the influence of RXR antagonist on the anti-inflammatory effect of PPARγ agonist pioglitazone in carrageenan test. In addition, we also examined the influence of PPAR antagonist on the anti-inflammatory effect induced by RXR agonist NEt-3IP. The RXR antagonist suppressed the antiedema effect of PPARγ agonist. In addition, the anti-inflammatory effect of RXR agonist was suppressed by PPARγ antagonist. PPARγ agonist-induced anti-inflammatory effects were reversed by the RXR antagonist. Thus, we showed that the endogenous RXR ligand might contribute to the PPARγ agonist-induced anti-inflammatory effect.

DOI： 10.1155/2011/840194

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The prophylactic use of anti-allergic drugs has been proposed to be effective in the treatment of seasonal allergic rhinitis in humans. However, there is little information regarding the prophylactic effect of thromboxane A(2) (TXA(2)) receptor antagonist on allergic rhinitis. Recent studies revealed that a TXA(2) receptor antagonist ramatroban could block the prostaglandin D(2) (PGD(2)) receptor and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). In the present study, we investigated the prophylactic effects of the histamine H(1) receptor antagonist epinastine and the TXA(2) receptor antagonist ramatroban and seratrodast on mouse models of allergic rhinitis. Female BALB/c mice were sensitized by an intraperitoneal injection of ovalbumin and alum on days 0, 5, 14 and 21. Seven days later, mice were sensitized by intranasal application of ovalbumin thrice a week. Drugs were administered once a day from day 22. The severity of allergic rhinitis was assessed by determining the extent of 2 nasal allergic symptoms (sneezing and nasal rubbing). Histamine sensitivity and eosinophil infiltration into the nasal mucosa were also determined. Epinastine and ramatroban significantly reduced nasal symptoms and the number of eosinophils in the nasal mucosa. Seratrodast showed no effect on nasal symptoms and eosinophil infiltration into the nasal mucosa. In addition, histamine sensitivity was reduced by epinastine and ramatroban. These results indicate that epinastine and ramatroban induce the prophylactic effect on allergic rhinitis.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pruritus is a common adverse effect of opioid treatment. However, the mechanism by which pruritus is induced by opioid administration is unclear. In this study, we examined the effects of the intradermal injection of loperamide, a peripherally restricted opioid receptor agonist, on the itch sensation. When injected intradermally into the rostral part of the back in mice, loperamide elicited scratching behavior. We also examined the effects of the selective mu opioid receptor agonist [d-Ala², N-Me-Phe⁴, Gly⁵-ol]-enkephalin acetate (DAMGO), the selective delta opioid receptor agonist [d-Pen(2,5)]-enkephalin (DPDPE), and the selective kappa opioid receptor agonist U-50488H on scratching behavior in mice in order to determine which subtype is involved in opioid-induced pruritus. Following intradermal injection into the rostral part of the back in mice, DAMGO elicited scratching behavior, while DPDPE and U-50488H did not. This suggests that peripheral mu opioid activation elicits the itch sensation. Next, we focused on the treatment of opioid-induced itch sensation without central adverse effects. Naloxone methiodide is a peripherally restricted opioid receptor antagonist. In the present study, naloxone methiodide significantly suppressed scratching behavior induced by loperamide and DAMGO. These findings suggest that mu opioid receptors play a primary role in peripheral pruritus and that naloxone methiodide may represent a possible remedy for opioid-induced itching.

DOI： 10.1016/j.ejphar.2010.07.039

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Previous studies have shown that peroxisome proliferator-activated receptor gamma (PPARgamma) is involved in allergic rhinitis. It has been reported that 5-aminosalicylate (5-ASA) has an affinity for PPARgamma, but the effects of 5-ASA on the nasal symptoms of allergic rhinitis are unclear. This study aimed to clarify the effects of 5-ASA on nasal symptoms in an allergic rhinitis model in mice. Female BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and aluminium hydroxide hydrate gel (alum) on days 0, 5, 14 and 21. Seven days later, mice were sensitized by the intranasal application of OVA thrice a week. 5-ASA was also administered orally after instillation of the antigen from day 28. The severity of allergic rhinitis was assessed by determining the extent of 2 nasal allergic symptoms-sneezing and nasal rubbing. In addition, serum OVA-specific immunoglobulin E (IgE) antibody, interleukin (IL)-4, and IL-10 levels in nasal lavage fluid and histamine sensitivity were determined. Repeated oral administration of 5-ASA attenuated the progression of nasal symptoms in sensitized mice in a dose-dependent manner. Additionally, 5-ASA prevented an increase in histamine sensitivity. Finally, 5-ASA inhibited both OVA-specific IgE antibody and IL-4 production; however, it had no effect on IL-10 levels. These results indicate that 5-ASA has a prophylactic effect on allergic rhinitis.

DOI： 10.1016/j.intimp.2010.03.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Itching is known as a commonly side effect of opioid administration. However, the relationship of opioid receptors to itching is unclear. In this study, we examined the effect of intradermal injection of morphine and fentanyl on the itching sensation. When injected intradermally into the rostral back of mice, morphine and fentanyl elicited scratching behavior. In addition, an opioid receptor antagonist, naloxone, and a peripherally restricted opioid receptor antagonist, naloxone methiodide, significantly suppressed morphine- and fentanyl-induced scratching behavior. Moreover, the morphine-induced scratching behavior was suppressed by histamine H(1) receptor antagonists, such as diphenhydramine, chlorpheniramine, epinastine and cetirizine. On the other hand, fentanyl-induced scratching behavior was not suppressed by histamine H(1) receptor antagonists. Additionally, scratching behavior induced by morphine and fentanyl were not suppressed by glucocorticoids (predonisolone and dexamethasone). In conclusion, opioid-induced itching may involve in peripheral opioid receptors. Moreover, histamine and arachidonic acid metabolites played no main role in opioid-induced scratching behavior.

DOI： 10.1016/j.ejphar.2009.10.066

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A benzensulfonanilide-type cyclooxygenase-1 (COX-1)-selective inhibitor, ZXX2-77: 4-amino-4'-chloro-N-methylbenzenesulfonanilide (4a), has been reported as a novel analgesic that does not cause gastric damage. This compound has a weak analgesic effect but has potent in vitro COX-1 inhibitory activity. Since the reason for the weak analgesic effect in vivo was thought to be the low rate of oral absorption, the blood concentration of ZXX2-77 (4a) was measured in rats. It was found that the C(max) value (1.2 microM) of ZXX2-77 (4a) at a dose of 30 mg/kg did not reach the COX-1 IC(50) value (3.2 microM). On the other hand, ZXX2-79 (4b) (SO(2)NH derivative of ZXX2-77 (4a); 4-amino-4'-chlorobenzenesulfonanilide), which shows less potent COX inhibitory activities (COX-1 IC(50) = 12 microM, COX-2 IC(50) = 150 microM) than those of ZXX2-77 (4a) in vitro, was found to be more absorbable (C(max) = 16 microM at a dose of 30 mg/kg in rats) than ZXX2-77 (4a). Furthermore, ZXX2-79 (4b) not only showed a potent analgesic effect in a formalin test but also caused little gastric damage. These findings indicate that demethylated sulfonamide compounds are more easily absorbed than are N-methylated sulfonamide compounds and suggest that COX-1-selective inhibitors will be useful as analgesics that do not cause gastric damage.

DOI： 10.1002/jps.21388

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The present study was performed to study the participation of histamine H(3) receptors in nasal symptoms using Sch 50971, a potent and selective agonist of the H(3) receptor. Repeated topical application of antigen caused an increase in sneezing and nasal rubbing in sensitized mice. Oral administration of Sch 50971 and imetit, specific H(3)-receptor agonists, resulted in an inhibition of nasal symptoms induced by an antigen similar to an H(1)-receptor antagonist, cetirizine. Furthermore, simultaneous use of H(3)-receptor agonists, Sch 50971 or imetit, and an H(1)-receptor antagonist, cetirizine, caused a significant inhibitory effect on nasal symptoms at doses that showed no effect when used separately. The number of eosinophils in the nasal mucosa of mice sensitized with antigen was significantly decreased by cetirizine; however, Sch 50971 and imetit had no effect on eosinophil infiltration. These results clearly indicate that H(3) receptors are involved in the etiology of nasal allergy, and the stimulation of H(3) receptors may be useful as a novel therapeutic approach in nasal allergy.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although cyclooxygenase-1 (COX-1) inhibition is thought to be a major mechanism of gastric damage by nonsteroidal anti-inflammatory drugs (NSAIDs), some COX-1-selective inhibitors exhibit strong analgesic effects without causing gastric damage. However, it is not clear whether their analgesic effects are attributable to COX-1-inhibitory activity or other bioactivities. Here, we report that N-(5-amino-2-pyridinyl)-4-(trifluoromethyl)benzamide ( 18f, TFAP), which has a structure clearly different from those of currently available COX-1-selective inhibitors, is a potent COX-1-selective inhibitor (COX-1 IC 50 = 0.80 +/- 0.05 microM, COX-2 IC 50 = 210 +/- 10 microM). This compound causes little gastric damage in rats even at an oral dose of 300 mg/kg, though it has an analgesic effect at as low a dose as 10 mg/kg. Our results show that COX-1-selective inhibitors can be analgesic agents without causing gastric damage.

DOI： 10.1021/jm701191z

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bmc.2007.01.059

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In order to create novel analgesic agents without gastric disturbance, structurally simple cyclooxygenase-1 (COX-1) inhibitors with a benzenesulfonanilide skeleton were designed and synthesized. As a result, compounds 11f and 15a, which possess a p-amino group on the benzenesulfonyl moiety and p-chloro group on the anilino moiety, showed COX-1-selective inhibition. Moreover compound 11f, which is the most potent compound in this study showed more potent analgesic activity than that of aspirin at 30 mg/kg by po. The anti-inflammatory activity and gastric damage, however, were very weak or not detectably different from aspirin. Since the structure of our COX-1 inhibitors are very simple, they may be useful as lead compounds for superior COX-1 inhibitors as analgesic agents without gastric disturbance.

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掲載種別：研究論文（学術雑誌）  

The participation of histamine H3 receptors in the regulation of skin vascular permeability changes in mast cell-deficient mice was studied. Although intradermal injection of histamine H3 antagonists, iodophenpropit and clobenpropit, at a dose of 100 nmol/site caused significant increases in skin vascular permeability in both mast cell-deficient (WBB6F1 W/Wv) and wild-type (WBB6F1 +/+) mice, this response was significantly lower in mast cell-deficient mice than in the wild-type controls. Histamine also caused dose-related increases in skin vascular permeability in both wild-type and mast cell-deficient mice. Significant effects were observed at doses of 10 and 100 nmol/site, and no significant difference in skin vascular permeability was observed between mast cell-deficient and wild-type mice. However, histamine contents of dorsal skin in mast cell-deficient mice were significantly lower than in wild-type mice. In addition, the H1 antagonists diphenhydramine and chlorpheniramine and the NK1 antagonists, L-732,138 and L-733,060, were able to antagonize H3 antagonist-induced skin vascular permeability. These results indicated that blockade of H3 receptors by H3 antagonists induce skin vascular permeability through mast cell-dependent mechanisms. In addition, histamine and, to a lesser extent substance P are involved in the reaction. © 2003 Published by Elsevier B.V.

DOI： 10.1016/S1567-5769(03)00009-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The participation of histamine H(3) receptors in the regulation of skin vascular permeability changes in mast cell-deficient mice was studied. Although intradermal injection of histamine H(3) antagonists, iodophenpropit and clobenpropit, at a dose of 100 nmol/site caused significant increases in skin vascular permeability in both mast cell-deficient (WBB6F1 W/W(v)) and wild-type (WBB6F1 +/+) mice, this response was significantly lower in mast cell-deficient mice than in the wild-type controls. Histamine also caused dose-related increases in skin vascular permeability in both wild-type and mast cell-deficient mice. Significant effects were observed at doses of 10 and 100 nmol/site, and no significant difference in skin vascular permeability was observed between mast cell-deficient and wild-type mice. However, histamine contents of dorsal skin in mast cell-deficient mice were significantly lower than in wild-type mice. In addition, the H(1) antagonists diphenhydramine and chlorpheniramine and the NK(1) antagonists, L-732,138 and L-733,060, were able to antagonize H(3) antagonist-induced skin vascular permeability. These results indicated that blockade of H(3) receptors by H(3) antagonists induce skin vascular permeability through mast cell-dependent mechanisms. In addition, histamine and, to a lesser extent substance P are involved in the reaction.

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掲載種別：研究論文（学術雑誌）  

Eosinophil infiltration into inflammatory tissues and the subsequent release of inflammatory mediators are the hallmarks of several inflammatory allergic diseases. Although there have been a considerable number of publications on anti-inflammatory effects of glucocorticoids, little is known about whether glucocorticoids affect the activation of eosinophils directly. We studied the effects of three glucocorticoids, mometasone furoate, dexamethasone and beclomethasone dipropionate, on superoxide generation and the chemotaxis of rat eosinophils. Highly purified rat eosinophils were treated for 6 h with mometasone furoate, dexamethasone or beclomethasone dipropionate. Eosinophils were stimulated with phorbol myristate acetate (PMA) for superoxide generation, while for induction of chemotaxis, platelet-activating factor (PAF) or leukotriene B4 (LTB4) was used. None of the glucocorticoids used in the present study caused significant suppressive effects on superoxide generation induced by PMA. On the other hand, both PAF- and LTB4-induced migration of rat eosinophils were inhibited in a concentration-dependent manner by glucocorticoids. Mometasone furoate showed a significant effect at concentrations higher than 10-11 M. Dexamethasone and beclomethasone dipropionate also caused a significant inhibition at concentrations higher than 10-8 and 10-7 M, respectively. These results indicated that the anti-inflammatory effects of glucocorticoids were mediated by direct inhibition of eosinophil migration. Furthermore, mometasone furoate was suggested to be more useful than the other drugs in the treatment of allergic diseases responsible for eosinophil chemotaxis. © 2003 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S1567-5769(03)00055-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Eosinophil infiltration into inflammatory tissues and the subsequent release of inflammatory mediators are the hallmarks of several inflammatory allergic diseases. Although there have been a considerable number of publications on anti-inflammatory effects of glucocorticoids, little is known about whether glucocorticoids affect the activation of eosinophils directly. We studied the effects of three glucocorticoids, mometasone furoate, dexamethasone and beclomethasone dipropionate, on superoxide generation and the chemotaxis of rat eosinophils. Highly purified rat eosinophils were treated for 6 h with mometasone furoate, dexamethasone or beclomethasone dipropionate. Eosinophils were stimulated with phorbol myristate acetate (PMA) for superoxide generation, while for induction of chemotaxis, platelet-activating factor (PAF) or leukotriene B(4) (LTB(4)) was used. None of the glucocorticoids used in the present study caused significant suppressive effects on superoxide generation induced by PMA. On the other hand, both PAF- and LTB(4)-induced migration of rat eosinophils were inhibited in a concentration-dependent manner by glucocorticoids. Mometasone furoate showed a significant effect at concentrations higher than 10(-11) M. Dexamethasone and beclomethasone dipropionate also caused a significant inhibition at concentrations higher than 10(-8) and 10(-7) M, respectively. These results indicated that the anti-inflammatory effects of glucocorticoids were mediated by direct inhibition of eosinophil migration. Furthermore, mometasone furoate was suggested to be more useful than the other drugs in the treatment of allergic diseases responsible for eosinophil chemotaxis.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The effects of anti-pruritic drugs on scratching behavior associated with passive cutaneous anaphylaxis in histamine H(1) receptor-deficient and wild-type mice were studied. Passive sensitization with mouse monoclonal anti-dinitrophenyl-immunoglobulin E (IgE) resulted in an increase in the incidence of scratching behavior induced by intravenous injection of dinitrophenyl-ovalbumin in both wild-type and histamine H(1) receptor-deficient mice. The histamine H(1) receptor antagonist diphenhydramine inhibited scratching behavior induced by antigen in passively sensitized wild-type mice, whereas no effect was observed in histamine H(1) receptor-deficient mice. On the other hand, oxatomide inhibited scratching behavior in both mice, although the effect in wild-type mice was more potent than that in histamine H(1) receptor-deficient mice. Tranilast inhibited scratching behavior with the same potency in both mice. We concluded that the scratching behavior associated with passive cutaneous anaphylaxis involves not only histamine H(1) receptors but also other chemical mediators. Furthermore, the results of the present study indicated that oxatomide has an antagonistic effect on histamine H(1) receptors as well as anti-pruritic effect in vivo.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We examined the effect of propolis granular A. P. C on lung tumorigenesis in female A/J mice. Lung tumors were induced by the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) administered in drinking water for 7 weeks in mice maintained on an AIN-76A semi-synthetic diet. Propolis granular A. P. C (100 mg/kg body wt.) was administered orally daily for 6 days/week from 1 week before NNK administration and throughout the experiment. Sixteen weeks after the NNK treatment, the mice were killed and the number of surface lung tumors was measured. The number of lung tumors in mice treated with NNK alone for 7 weeks (9.4 mg/mouse) was significantly more than in that observed in control mice. Propolis granular A. P. C significantly decreased the number of lung tumors induced by NNK. These results indicate that propolis granular A. P. C is effective in suppressing NNK-induced lung tumorigenesis in mice.

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掲載種別：研究論文（学術雑誌）  

To clarify the role of mucosal mast cells in the lesion sites of colitis induced by dextran sulfate sodium (DSS) in rats, we investigated the histological changes and alterations relevant to mucosal mast cells in the spontaneous recovery process of colitis. Oral administration of 4% DSS solution for 11 days resulted in surface epithelial loss, crypt loss and goblet cell depletion in the rectal mucosa. A marked infiltration of inflammatory cells into the mucosa, which was consistent with a significant increase in myeloperoxidase (MPO) activity, was observed. In addition, mucosal mast cell number and rat mast cell protease (RMCP) I and II levels in the rectum increased at day 0 after DSS treatment, and most of the mucosal mast cells were degranulated. After replacing 4% DSS solution with water, re-epithelialization and restoration of goblet cells were observed at day 5 and day 10, respectively, but crypt damage was hardly recovered even at day 20. The elevated myeloperoxidase activity was significantly decreased from day 5 after DSS treatment. The increased number of mucosal mast cells was further elevated up to about 1.5-fold at day 10 and day 20 after DSS treatment and little degranulation was observed. In the spontaneous recovery process, the increased rat mast cell protease II level in the rectum was maintained for 20 days, while the increased rat mast cell protease I level was gradually decreased and recovered to control level. These results suggest that proliferated mucosal mast cells remained for 20 days, although most of infiltrated inflammatory cells disappeared in spontaneous recovery process of colitis. It may therefore be presumed that proliferated mucosal mast cells play a role in spontaneous recovery process of the colitis induced by DSS. © 2003 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S1567-5769(02)00299-0

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掲載種別：研究論文（学術雑誌）  

The effects of [Arg8]-vasopressin (AVP) and related compounds on regional cerebral blood flow (rCBF) in the hippocampus were studied using conscious spontaneously hypertensive rats (SHR). rCBF in the hippocampus decreased gradually with age in proportion to an increase in mean blood pressure. Subcutaneous injection of AVP caused a dose-dependent increase in rCBF in the hippocampus. The effects of the metabolic fragments AVP4-9 and AVP4-8 on rCBF were relatively weak. OPC-31260, a vasopressin V2 antagonist, antagonized the AVP-induced increase in rCBF in the hippocampus. Furthermore, subcutaneous injection of DDAVP, a V2 agonist, increased rCBF in the hippocampus. On the other hand, the AVP-induced increase in rCBF in the hippocampus was not antagonized by OPC-21268, a vasopressin V1 antagonist. Intracerebroventricular injection of AVP caused no significant changes in rCBF in the hippocampus, even at a dose of 10 ng/site. © 2003 Prous Science. All rights reserved.

DOI： 10.1358/mf.2003.25.3.769639

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掲載種別：研究論文（学術雑誌）  

We examined the effect of propolis granular A. P. C on lung tumorigenesis in female A/J mice. Lung tumors were induced by the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) administered in drinking water for 7 weeks in mice maintained on an AIN-76A semi-synthetic diet. Propolis granular A. P. C (100 mg/kg body wt.) was administered orally daily for 6 days/week from 1 week before NNK administration and throughout the experiment. Sixteen weeks after the NNK treatment, the mice were killed and the number of surface lung tumors was measured. The number of lung tumors in mice treated with NNK alone for 7 weeks (9.4 mg/mouse) was significantly more than in that observed in control mice. Propolis granular A. P. C significantly decreased the number of lung tumors induced by NNK. These results indicate that propolis granular A. P. C is effective in suppressing NNK-induced lung tumorigenesis in mice. © 2003 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0304-3835(03)00016-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We examined the participation of the NMDA receptor in the histaminergic system using radial maze performance in Zucker rats. Although pyrilamine caused a significant effect on spatial memory deficit in lean rats, no significant spatial memory deficit was observed in obese rats. On the other hand, MK-801 caused significant spatial memory deficits in obese rats in comparison with lean rats. These results indicate that the histaminergic neuron is not closely related with the radial maze performance in obese rats. In addition, the potent effect of MK-801 observed in obese rats compared with lean rats may be responsible for the activation of NMDA receptors in obese rats.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The purpose of this study was to investigate the involvement of chemical mediators other than histamine in nasal allergic signs using histamine H(1) receptor-deficient mice. In passively sensitized mice, antigen instillation into the nasal cavity induced significant increases in sneezing and nasal rubbing in wild-type mice, but no such increases were observed in histamine H(1) receptor-deficient mice. In actively sensitized mice, both sneezing and nasal rubbing were also significantly increased in a dose-dependent manner in both wild-type and histamine H(1) receptor-deficient mice. Histamine H(1) receptor antagonists such as cetirizine and epinastine significantly inhibited antigen-induced nasal allergic signs in wild-type mice, although the effects were incomplete. In addition, the thromboxane A(2) receptor antagonist ramatroban also inhibited these responses in wild-type mice. However, the leukotriene receptor antagonist zafirlukast showed no effects in wild-type mice. These results suggested that in the acute allergic model (passive sensitization), only histamine H(1) receptors are related to nasal signs induced by antigen, whereas in the chronic allergic model (active sensitization), both histamine H(1) receptors and thromboxane A(2) receptors were involved in the responses.

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掲載種別：研究論文（学術雑誌）  

Effect of docosahexaenoic acid (DHA) [22:6(n-3)]-fortified Chlorella oil fraction on radial maze performance was studied in aged mice. Male ICR mice aged 9 months were fed a diet containing 2 g DHA-fortified Chlorella oil fraction/100 g diet or normal diet (Control group) for 2 months. Two months after the start of feeding, the mice were tested for learning ability related to 2 types of memory, reference memory and working memory, with the partially (4 of 8) baited eight-arm radial maze. Reference memory is a kind of information that should be retained until the next trial. Working memory is a kind of information that disappears in a short time. Entry into the unbaited arms and repeated entry into the visited arms were defined as reference memory errors and working memory errors, respectively. DHA-fortified Chlorella oil fraction administration to mice for 2 months resulted in a significant decrease in the number of working memory errors without affecting the number of reference memory errors. A significant increase in the DHA content in the brain was also observed. These results suggest that the intake of DHA-fortified Chlorella oil fraction effectively enhances working memory in maze performance.

DOI： 10.1248/bpb.25.1090

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The role of histamine H1 receptors in nasal allergic symptoms (sneezing and nasal rubbing) were studied using histamine H1 receptor-deficient mice. Intranasal instillation of histamine solution resulted in significant increases in sneezing and nasal rubbing in wild-type mice, whereas no increases were observed in histamine H1 receptor-deficient mice. The histamine H1 receptor agonist 2-pyridylethylamine induced sneezing and nasal rubbing in a dose-dependent-manner in wild-type mice, but no such increase was found in histamine H1 receptor-deficient mice. On the other hand, the histamine H2 receptor agonist dimaprit did not increase sneezing and nasal rubbing in wild-type mice. Histamine H1 receptor antagonists such as chlorpheniramine and epinastine significantly inhibited nasal allergic symptoms caused by histamine, but the histamine H2 receptor antagonists cimetidine and famotidine showed no effect. No additional effects were observed by combined use of chlorpheniramine and cimetidine or famotidine compared with cimetidine or famotidine alone. These results suggested that histamine H1 receptors play an important role in nasal allergy symptoms induced by histamine.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We examined the effects of a histidine-deficient diet on brain histamine contents as well as on learning and memory using the eight-arm radial maze in rats. A significant decrease in histamine content in the hippocampus was observed after long-term feeding of rats with a histidine-deficient diet. At the same time, significant enhancement of the acquisition process in radial maze performance was also observed. Pyrilamine did not show a significant effect on radial maze performance in histidine-deficient rats. On the other hand, pyrilamine caused a significant spatial memory deficit in control rats. Scopolamine was effective in inhibiting spatial memory in both histidine-deficient and control rats. MK-801 caused spatial memory deficits more potently in histidine-deficient rats than in controls. Brain glycine contents showed a significant increase in the hippocampus in histidine-deficient rats. These results indicated that the spatial memory deficits induced by MK-801 in histidine-deficient rats are closely related to increased glycine levels and activation of NMDA receptors.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Six flavonoid glycosides, eriocitrin (1), narirutin (2), hesperidin (3), luteolin-7-O-rutinoside (4), isorhoifolin (5), diosmin (6), rosmarinic acid (7) and 5,7-dihydroxycromone-7-O-rutinoside (8), were isolated from the aerial part of Mentha piperita L. Among these compounds, compound 4 showed a potent inhibitory effect on histamine release induced by compound 48/80 and antigen-antibody reaction. This compound was more effective than luteolin and luteolin-7-O-glucoside in inhibiting histamine release from rat peritoneal mast cells. Compound 4 also caused a dose-related inhibition of the antigen-induced nasal response and significant effects were observed at doses of 100 and 300 mg/kg. These results indicate that compound 4 may be clinically useful in alleviating the nasal symptoms of allergic rhinitis.

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掲載種別：研究論文（学術雑誌）  

We investigated the participation of mast cells in colitis inflammation induced by dextran sulfate sodium (DSS). The damage score and myeloperoxidase (MPO) activity were measured to confirm the occurrence of colitis. Rat mast cell protease (RMPCP) II levels in the serum were estimated as an index of mast cell degranulation. Tissue RMCP I and RMCP II levels in the rectum were also measured as markers of the numbers of connective tissue mast cells (CTMCs) and mucosal mast cells (MMCs), respectively. Administration of 4% DSS resulted in time-related increases in damage score, MPO activity and serum RMCP II levels, which were statistically significant at 7 and 11 days after treatment. Tissue RMCP I and RMCP II levels in the rectum were also increased significantly at 7 and 11 days, and 11 days, respectively after free drinking of 4% DSS. These results suggested that mast cells proliferated or the amount of protease per mast cell increased in the sites of inflammation induced by DSS, and that these mast cells may modulate the disorders observed in DSS-induced colitis. © 2002 Prous Science. All rights reserved.

DOI： 10.1358/mf.2002.24.1.677122

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掲載種別：研究論文（学術雑誌）  

The changes in membrane potential induced by compound 48/80 were studied using rat peritoneal mast cells. The mean resting membrane potential of rat mast cells was -12.3 ± 0.7 mM. When compound 48/80 was added to the mast cells, the cells were degranulated approximately 120 sec after the addition of the drug, after which immediate depolarization occurred. Degranulation of mast cells was not observed, even under the depolarization or hyperpolarization conditions caused by the replacement of a high K+ medium or the removal of K+ from the medium, respectively. Under both conditions, when compound 48/80 was added to the mast cells, degranulation was observed. Abrupt and marked depolarization was induced 30-60 sec after compound 48/80 was added. In addition, repolarization followed by gradual depolarization was observed without degranulation in mast cells treated with cytochalasin D after the addition of compound 48/80. These results suggest that the mast cells were depolarized by compound 48/80 independently of degranulation. It is also feasible that the gradual depolarization and repolarization induced by compound 48/80 in mast cells pretreated with cytochalasin D participated in the extracellular Na+ and Na+/K+-pump, respectively. © 2002 Prous Science. All rights reserved.

DOI： 10.1358/mf.2002.24.5.802303

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掲載種別：研究論文（学術雑誌）  

The role of histamine H1 receptors in nasal allergic symptoms (sneezing and nasal rubbing) were studied using histamine H1 receptor-deficient mice. Intranasal instillation of histamine solution resulted in significant increases in sneezing and nasal rubbing in wild-type mice, whereas no increases were observed in histamine H1 receptor-deficient mice. The histamine H1 receptor agonist 2-pyridylethylamine induced sneezing and nasal rubbing in a dose-dependent manner in wild-type mice, but no such increase was found in histamine H1 receptor-deficient mice. On the other hand, the histamine H2 receptor agonist dimaprit did not increase sneezing and nasal rubbing in wild-type mice. Histamine H1 receptor antagonists such as chlorpheniramine and epinastine significantly inhibited nasal allergic symptoms caused by histamine, but the histamine H2 receptor antagonists cimetidine and famotidine showed no effect. No additional effects were observed by combined use of chlorpheniramine and cimetidine or famotidine compared with cimetidine or famotidine alone. These results suggested that histamine H1 receptors play an important role in nasal allergy symptoms induced by histamine. © 2002 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S1567-5769(02)00010-3

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掲載種別：研究論文（学術雑誌）  

The effects of [Arg8] vasopressin on histamine H1 receptor antagonist-induced memory deficits were investigated using the eight-arm radial maze performance test in rats. Pyrilamine and diphenhydramine as well as scopolamine induced memory deficits characterized by increases in the number of total errors, reference memory errors and working memory errors. [Arg8] vasopressin improved not only scopolamine-but also pyrilamine-and diphenhydramine-induced memory deficits, although a high dose of [Arg8] vasopressin was needed to antagonize pyrilamine-induced memory deficits. The effects of pyrilamine on the brain [Arg8] vasopressin content were studied, and the hippocampus [Arg8] vasopressin content was shown to be decreased after pyrilamine injection. From these observations, it seems likely that [Arg8] vasopressin participates in not only the cholinergic system but also the histaminergic system in spatial memory. © 2001 Elsevier Science B.V.

DOI： 10.1016/S0014-2999(01)01080-9

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掲載種別：研究論文（学術雑誌）  

The present study was carried out to clarify the effects of extracts of the leaves of Mentha piperita L. on experimental allergic rhinitis. The 50% EtOH extract of peppermint inhibited histamine release from rat peritoneal mast cells induced by compound 48/80. The effect was dose-dependent and significant inhibition was observed at a concentration of 3 μg/ml. In addition, the 50% EtOH eluate separated from the 50% EtOH extract of peppermint by column chromatography (DIAION HP-20) was also effective in inhibiting histamine release at a concentration of 1 μg/ml. Nasal symptoms, sneezing and nasal rubbing induced by antigen challenge in actively sensitized rats were inhibited by oral administration of the 50% EtOH eluate. Significant inhibition of sneezing and nasal rubbing was observed at doses of 300 and 1000 mg/kg, p.o., respectively. Furthermore, the 50% EtOH eluate inhibited dye leakage into the nasal cavity of rats induced by antigen in a dose-dependent manner. These results suggested that extracts of Mentha piperita L. may be clinically effective in alleviating the nasal symptoms of allergic rhinitis.

DOI： 10.1248/bpb.24.92

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掲載種別：研究論文（学術雑誌）  

We investigated the effects of histidine on spatial memory deficits induced by the 5-HT1A-receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Working memory deficits were elicited by 8-OH-DPAT without affecting reference memory. Histidine improved the working memory deficit induced by 8-OH-DPAT at doses causing a significant increase in brain histamine content. This finding suggests that the histaminergic system regulates 8-OH-DPAT-induced working memory deficit.

DOI： 10.1254/jjp.86.451

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：ELSEVIER SCIENCE BV  

We investigated the role of mast cells in the sites of inflammation in colitis induced by dextran sulfate sodium (DSS). Haematoxylin and eosin staining revealed a marked infiltration of inflammatory cells and oedematous changes in mucosa and submucosa after drinking of 4% DSS. And, toluidine blue staining also revealed that the number of mast cells was increased after free drinking of 4% DSS. These results suggest that mast cells may modulate the disorder of DSS-induced colitis.

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：ELSEVIER SCIENCE BV  

To clarify the role of endogenous histamine in learning and memory, the effects of a-fluoromethylhistidine (FMH) on active avoidance response and spatial cognition were investigated in rats. Both intraperitoneal (i.p.) and intracerebro-ventricular (i.c.v.) injection of FMH caused a significant prolongation of the response latency in active avoidance response. FMH also showed spatial memory deficits characterized by an increase in the number of total errors and a decrease in the number of initial correct response. There was high correlation between the memory deficit and a decrease in the brain histamine content.

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掲載種別：研究論文（学術雑誌）  

In the present study, we have demonstrated that multiple first-generation H1-antagonists caused behavioral and EEG seizures in rats. The epileptogenic property of pyrilamine was more potent than either chlorpheniramine or diphenhydramine. In contrast, the second-generation H1-antagonists, loratadine and ebastine did not induce detectable epileptogenic activity. Intraperitoneal injection of histidine inhibited the EEG seizures induced by pyrilamine, diphenhydramine or chlorpheniramine; however no antagonism was observed with physostigmine. These results clearly suggest that the epileptogenic activity of first-generation H1-antagonists is dependent upon a centrally acting histaminergic mechanism. © 2000 Elsevier Science B.V.

DOI： 10.1016/S0006-8993(00)03041-9

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掲載種別：研究論文（学術雑誌）  

To clarify the role of histamine H1 receptors in allergic conjunctivitis, changes in vascular permeability of the conjunctiva were measured in histamine H1 receptor deficient mice. Wild-type mice showed a significant increase in vascular permeability of the conjunctiva induced by histamine. However, no such increase was found in histamine H1 receptor deficient mice. On the other hand, no differences were observed between wild-type and histamine H1 receptor deficient mice in response to serotonin. A significant increase in vascular permeability was observed in actively sensitized wild-type mice, whereas no increase was observed in histamine H1 receptor deficient mice. Similar findings were noted in passively sensitized animals. Histamine contents of the conjunctiva were significantly decreased by topical application of antigen in both wild-type and histamine H1 receptor deficient mice after active sensitization with antigen. These findings suggested that vascular permeability in the conjunctiva in allergic conjunctivitis is entirely regulated through histamine H1 receptor. (C) 2000 Elsevier Science B.V.

DOI： 10.1016/S0014-2999(00)00863-3

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掲載種別：研究論文（学術雑誌）  

The effects of mometasone furoate on experimental allergic rhinitis in rats were studied in comparison with that of fluticasone propionate. Topical application of both drugs inhibited dose-dependently the increase of nasal symptoms (sneezing and nasal rubbing) after antigen challenge to the nasal cavity of actively sensitized rats. Mometasone furoate and fluticasone propionate at concentrations of 0.01 or 0.1% significantly inhibited both nasal rubbing and sneezing 1 h after topical application of both drugs. The relative potencies of mometasone furoate in nasal rubbing and sneezing compared to fluticasone propionate were 5.01 and 6.87, respectively. Mometasone furoate (0.02%) and fluticasone propionate (0.1%) significantly inhibited the increase of antigen-induced nasal rubbing even 6 h after topical application, indicating that both drugs have a long-lasting effect. Copyright (C) 2000 S. Karger AG, Basel.

DOI： 10.1159/000028386

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掲載種別：研究論文（学術雑誌）  

An animal model of chronic allergic rhinitis was developed by repeated local booster sensitization into the nasal cavity in sensitized rats. The severity of allergic rhinitis was assessed by determining the extent of two markers of nasal allergic symptoms (sneezing and nasal rubbing) after antigen challenge. The number of incidents of sneezing and nasal rubbing was markedly increased during intranasal instillation of antigen in sensitized rats. The PCA titers were also markedly elevated by intranasal sensitization. Some histamine H1-receptor antagonists such as chlorpheniramine, ketotifen, astemizole and epinastine inhibited the increase in antigen-induced nasal symptoms in a dose-related manner. Nasal rubbing was more potently inhibited by H1-receptor antagonists than sneezing.In conclusion, we developed a chronic allergic rhinitis model showing nasal symptoms in rats, and this model may be useful for evaluating the effects of drugs on allergic rhinitis. Copyright (C) 2000 Elsevier Science B.V.

DOI： 10.1016/S0162-3109(00)00173-9

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掲載種別：研究論文（学術雑誌）  

We report a new experimental allergic conjunctivitis with Japanese cedar pollen as antigen in guinea pigs, and the immunological characteristics of this model were also elucidated. Allergic conjunctivitis was developed by immunization in guinea pigs with a mixture containing Japanese cedar pollen and killed Bordetella pertussis. When local application of Japanese cedar pollen suspension 14 d after systemic immunization was performed every 3 d, remarkable conjunctivitis was observed from 20 to 35d. Increase in vascular permeability and decrease in histamine contents of the conjunctiva were also observed after local application of antigen. Passive cutaneous anaphylactic (PCA) reactions revealed that both IgG- and IgE-rich antibodies were produced in this model. Chlorpheniramine, ketotifen and levocabastine were effective in inhibiting cedar pollen-induced conjunctivitis. Although a high concentration was needed, tranilast and amlexanox also showed significant inhibition of conjunctivitis induced by cedar pollen.

DOI： 10.1248/bpb.23.566

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掲載種別：研究論文（学術雑誌）  

The effects of metabolic fragments of [Arg8]-vasopressin (AVP), [pGlu4, Cyt6]AVP (AVP4-9), and desglycinamide-[pGlu4, Cyt6]AVP (AVP4-8) on the growth of hippocampal neurons in culture were investigated in comparison with those of AVP. AVP4-9 caused a significant increase in filopodial length following 96 h of exposure at concentrations higher than 300 nM. AVP4-9 was more potent than AVP. AVP4-8 also induced an increase in filopodial length, but this effect was less than that of AVP. The selective V1 agonist [Phe2, Ile3, Orn8]-vasopressin caused a significant increase in filopodial length, whereas the selective V2 agonist [deamino-Cys1, D-Arg8]-vasopressin showed no such effect. OPC-21268, a vasopressin V1 antagonist, blocked AVP and AVP fragment-induced increases in filopodial length. However, the V2 antagonist OPC-31260 showed no such effect. A23187, a representative Ca ionophore, also increased filopodial length, and the A23187-induced increase in filopodial length was potentiated by AVP and AVP fragments. These results indicated that AVP4-9 and AVP4-8 increased filopodial length in cultured hippocampal neurons by activating V1 receptors. Both phenomena induced by AVP4-9 and AVP4-8 were associated with intracellular calcium mobilization. Copyright (C) 2000 Elsevier Science Inc.

DOI： 10.1016/S0361-9230(99)00249-X

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掲載種別：研究論文（学術雑誌）  

The present study was performed to clarify the mechanism responsible for the drowsiness caused by first generation H1 antagonists according to electroencephalogram activity. All H1 antagonists used in the present study caused the EEG-recorded drowsiness pattern, i.e., increases in EEG power spectra of the δ and θ bands at the frontal cortex in rats. The potency of cyproheptadine was greater than those of diphenhydramine and promethazine, while that of pyrilamine was less than those of the other drugs examined. The increase in EEG power spectra in the δ band induced by H1 antagonists was antagonized by pretreatment with both histidine and physostigmine. The effect of pyrilamine was more potently antagonized by histidine and less potently antagonized by physostigmine as compared to diphenhydramine, promethazine and cyproheptadine. The increases in EEG power spectra induced by H1 antagonists were neither antagonized nor potentiated by 5-hydroxytryptophan. These results clearly indicate that the increases in EEG power spectra in the δ and θ bands at the frontal cortex in rats induced by first generation H1 antagonists are responsible for both histaminergic and cholinergic mechanisms. (C) 2000 Prous Science.

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掲載種別：研究論文（学術雑誌）  

The effects of GABAmimetic drugs on inhibition of amygdaloid kindled seizures induced by clobenpropit were investigated to clarify the relationship between histaminergic and GABAergic systems in seizures. I.p. injection of clobenpropit caused dose-dependent inhibition of amygdaloid kindled seizures. GABAmimetic drugs such as diazepam, sodium valproate and muscimol also inhibited amygdaloid kindled seizures in a dose-dependent manner. Diazepam at doses of 0.2 and 0.5 mg/kg, which showed no significant effect on amygdaloid kindled seizures when used separately, significantly potentiated the effect of clobenpropit. Similar findings were observed with sodium valproate and muscimol at doses of 100 mg/kg and 5 ng, respectively, although neither showed any significant effects when administered separately. Bicuculline caused significant antagonism of the inhibition of amygdaloid kindled seizures induced by clobenpropit, while the effect of diazepam was not antagonized by diphenhydramine. These results suggested that inhibition of amygdaloid kindled seizures induced by histamine is closely associated with the actions of GABA.

DOI： 10.1254/jjp.82.48

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掲載種別：研究論文（学術雑誌）  

The effects of Fujibitol, a preparation of crude drugs in wide clinical use for treatment of chronic rhinitis and empyema, on experimental allergic rhinitis in rats were studied. Fujibitol inhibited nasal allergic symptoms, i.e. sneezing and nasal rubbing, induced by antigen in sensitized animals. An increase in dye leakage into the nasal cavity induced by antigen was also inhibited by Fujibitol. On the other hand, no inhibitory effects were observed on either the nasal allergic symptoms or increase in dye leakage into the nasal cavity induced by histamine. However, Fujibitol was effective in inhibiting histamine release from the nasal cavity induced by antigen. Oxatomide used as positive control drug showed potent inhibitory effects on nasal symptoms and dye leakage into the nasal cavity induced by histamine and antigen. These results suggested that Fujibitol showed a remarkable protective effect against experimental rhinitis induced by antigen via inhibition of histamine release from the nasal cavity.

DOI： 10.1248/bpb.23.1055

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掲載種別：研究論文（学術雑誌）  

We examined influences of certain antibiotics on the release of chemical mediators from isolated rat peritoneal mast cells in vitro. Isolated peritoneal mast cells were obtained from male Wistar strain rats. Everninomicin (0.06 - 1.2 mg/ml), vancomycin (0.05 - 1.0 mg/ml), teicoplanin (0.07 - 1.4 mg/ml) and concanavalin A (0.01 mg/ml) were used. Isolated mast cells were incubated in the presence of various concentrations of the test compound at 37°C for 10 min. Histamine contents of the supernatant and cell pellet were measured by an automated fluorometric method. Prostaglandin D2 (PGD2) contents of the supernatant were determined by enzyme immunoassay. Everninomicin (0.06 - 1.2 mg/ml) had no influence on histamine and PGD2 release from mast cells. On the other hand, vancomycin significantly released both histamine (0.5 and 1.0 mg/ml) and PGD2 (1.0 mg/ml) from mast cells, but vancomycin did not affect concanavalin A-induced histamine and PGD2 release. Teicoplanin (more than 0.07 mg/ml) significantly stimulated histamine and PGD2 release from mast cells and it also significantly potentiated concanavalin A-induced histamine and PGD2 release. These results suggest that everninomicin causes no chemical mediator release from mast cells, different from vancomycin and teicoplanin.

DOI： 10.1254/jjp.83.300

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掲載種別：研究論文（学術雑誌）  

The preventive effect of propolis extract on D-galactosamine-induced hepatic injury was examined in rats. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly increased at 24 h after intraperitoneal injection of D-galactosamine (400 mg/kg) in the animals. Propolis extract was administered orally three times in doses of 3 or 30 mg/kg at 18 h and 1 h before and 8 h after D-galactosamine injection. The extract itself and the vehicle alone (dextran) caused no significant changes in serum AST or ALT activities. Treatment with the extract dose- dependently prevented the increases in serum AST and ALT activities induced by D-galactosamine, and significant inhibition was observed at a dose of 30 mg/kg. These results suggested that propolis extract may have an ameliorating effect on hepatic dysfunction.

DOI： 10.1248/bpb.22.1237

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掲載種別：研究論文（学術雑誌）  

The effects of α-fluoromethylhistidine (α-FMH) on spatial cognition were investigated using the eight-arm radial maze paradigm in rats. Intracerebroventricular (ICV) injection of α-FMH resulted in spatial memory deficits characterized by an increase in the number of total errors (TE) and a decrease in the number of initial correct responses (ICR). There was a strong correlation between increases in the number of TE and decreases in histamine contents of the cortex and hippocampus regions of the brain, which are known to participate in learning and memory. On the other hand, both histamine (50-100 ng, ICV) and thioperamide (10 μg, ICV) significantly ameliorated the memory deficit induced by α-FMH. However, metoprine showed no significant effect on the α-FMH-induced memory deficit. Pyrilamine and R-(α)-methylhistamine enhanced the memory deficit induced by α-FMH, at doses that had no appreciable effect when administered alone. In contrast, no significant influence on α-FMH-induced memory deficit was observed with zolantidine. Copyright (C) 1999 Elsevier Science Inc.

DOI： 10.1016/S0091-3057(99)00128-8

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掲載種別：研究論文（学術雑誌）  

The present study was performed to see if first-generation histamine H1-antagonists are useful sedative-hypnotic drugs. Increases in electroencephalogram (EEG) power spectra of the delta band (0-4 Hz) at the frontal cortex and theta band (4-8 Hz) at the hippocampus in rats were used as an indexes of sleep. The H1-antagonists used in this study resulted in a decrease in sleep latency and an increase in sleep duration (slow wave sleep). The rate of REM (rapid eye movement) sleep during slow wave sleep was decreased by H1-antagonists and brotizolam. The order of potency of H1- antagonists for the reduction in sleep latency (from greatest to least) was promethazine>chlorpheniramine>diphenhydramine and pyrilamine, and that for the increase in sleep duration was chlorpheniramine>promethazine>diphenhydramine and pyrilamine. Brotizolam was more potent than these H1-antagonists, with 14-18-fold and 4-14-fold greater effects on sleep latency and duration, respectively. These results clearly show that H1-antagonists are effective in mild to moderate insomnia as sedative-hypnotic drugs.

DOI： 10.1248/bpb.22.1079

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掲載種別：研究論文（学術雑誌）  

The effects of histamine on the spatial memory deficits induced by MK- 801 were investigated using the eight-arm radial maze paradigm in rats. Intracerebroventricular (i.c.v.) injection of histamine or thioperamide, and intraperitoneal (i.p.) injection of histidine improved the spatial memory deficits induced by MK-801. Similar results were obtained with 2- thiazolylethylamine. In contrast, 4-methylhistamine showed no significant effect. Based on these observations, it seems likely that the protective effect of histamine on MK-801-induced spatial memory deficit is mediated by H1-receptors.

DOI： 10.1016/S0006-8993(99)01739-4

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掲載種別：研究論文（学術雑誌）  

Changes in intracellular Ca2+ concentration ([Ca2+](i)) induced by [Arg8]-vasopressin (AVP) were studied in cultured rat hippocampal neurons by fura-2 fluorometry. AVP (10-1,000 nM) caused a dose-dependent increase in [Ca2+](i). The selective V1 vasopressin receptor agonist [Phe2, Ile3, Orn8]vasopressin also induced a significant increase in [Ca2+](i), whereas the selective V2 vasopressin receptor agonist [deamino Cys1, D-Arg8]- vasopressin showed no effect. The AVP-induced increase in [Ca2+](i) was inhibited by the selective V1 vasopressin receptor antagonist d(CH2)5[Tyr2(Me), Arg8]-vasopressin and nonpeptide V1 antagonist OPC- 21268. On the other hand, no antagonistic effects were observed with the V2 vasopressin antagonist desglycinamide-[d(CH2)5, D-Ile2, Ile4, Arg8]- vasopressin and nonpeptide V2 antagonist OPC-31260. The increase in [Ca2+](i) induced by AVP was abolished after removal of extracellular Ca2+. In addition, AVP-induced [Ca2+](i) elevation was not affected by treatment with verapamil, which blocked the [Ca2+](i) increase induced by an isotonic high K+- medium (50 mM). However, ω-conotoxin GVIA completely inhibited the effect of AVP. These results suggested that the AVP-induced [Ca2+](i) increase in cultured rat hippocampal neurons is due to influx of Ca2+ through V1 VP receptors coupled with N-type calcium channels.

DOI： 10.1016/S0361-9230(99)00064-7

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掲載種別：研究論文（学術雑誌）  

The effects of Fujibitol, a remedy for the nasal symptoms of immediate and delayed type allergic reactions were studied. Fujibitol inhibited active systemic anaphylaxis in mice, heterologous passive cutaneous anaphylaxis (PCA) in rats, Masugi's nephritis in rats and delayed type hypersensitivity induced by picryl chloride in mice, but did not affect homologous PCA or immune complex-induced glomerulonephritis in rats. These results suggested that Fujibitol is effective for treatment of allergy-induced inflammation since IgG and type IV allergic reactions were inhibited.

DOI： 10.1358/mf.1999.21.5.541913

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掲載種別：研究論文（学術雑誌）  

The effects of levocabastine, a novel histamine H1-receptor antagonist, on lipid mediator release induced by antigen-antibody reaction from actively sensitized guinea pig lung fragments were studied. Levocabastine dose-dependently inhibited the release of leukotriene C4 from guinea pig lung fragments induced by antigen. A significant effect was observed with levocabastine at a concentration of 10-4 M. On the other hand, levocabastine produced no effect on the release of leukotriene E4 or thromoboxane B2. From these findings, it was concluded that levocabastine may be useful for relieving the nasal obstruction in allergic rhinitis caused by inhibition of leukotriene C4 release.

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掲載種別：研究論文（学術雑誌）  

The present study was undertaken to clarify whether or not diphenhydramine is useful for sedative-hypnotic drug. EEG power spectra of delta band (0-4 Hz) at the frontal cortex in rats was used for an index of sleep. Diphenhydramine at doses of 2-20mg/kg, p.o. caused a dose-dependent shortening of sleep latency and prolongation of sleep duration. Significant effect was observed at a dose of 10mg/kg or more. These effects were almost the same as those of chlorpheniramine and less than those of brotizolam. The results clearly indicate that diphenhydramine is effective sedative-hypnotic drug for mild insomnia.

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掲載種別：研究論文（学術雑誌）  

The effects of histamine and related compounds on regional cerebral blood flow (rCBF) in the hippocampus of conscious rats were studied. Intracerebroventricular injection of histamine caused a dose-dependent increase in rCBF in the hippocampus, and similar findings were observed with not only the H1 agonist, 2-thiazolylethylamine, but also the H2 agonist, dimaprit. Intraperitoneal injection of L-histidine also resulted in an increase in rCBF in the hippocampus, in parallel with elevation of histamine content in the brain. The increase in rCBF in the hippocampus induced by L- histidine was antagonized by both H1 and H2 antagonists (diphenhydramine, pyrilamine and zolantidine). In addition, when both antagonists were injected simultaneously, an additive effect was observed in antagonism of the L- histidine-induced increase in rCBF. L-Histidine caused no marked changes in blood pressure even at a dose of 1,500 mg/kg, which showed an increase in rCBF in the hippocampus. These results indicate that histamine elicited an increase in rCBF via both H1 and H2 receptors.

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掲載種別：研究論文（学術雑誌）  

1. Effects of anti-Parkinsonian drugs on neurobehavioural changes induced by bilateral lesions of dopaminergic neurons were investigated in rats. 2. Dopaminergic neurons in rats were lesioned bilaterally by injection of 6-hydroxydopamine (6-OHDA; 8 μg) into the medial forebrain bundle at the level of the posterolateral hypothalamus. As a result, a decrease in locomotor activity and marked catalepsy and prolongation of grasping time were observed. 3. Levodopa, talipexole, bromocriptine and theophylline dose- dependently antagonized the decrease in locomotor activity induced by bilateral 6-OHDA lesions. These drugs also showed antagonistic effects on the appearance of catalepsy and prolongation of grasping time induced by bilateral 6-OHDA lesions. In contrast, trihexyphenidyl showed no antagonizing effect on the neurobehavioural changes induced by 6-OHDA lesions at any concentration tested. 4. Combined treatment with levodopa and talipexole antagonized the neurobehavioural changes induced by bilateral 6-OHDA lesions, whereas no marked changes were observed when either drug was administered separately. The same findings were noted with the simultaneous use of either levodopa (2 mg/kg) and theophylline (2 mg/kg) or talipexole (0.005 mg/kg) and theophylline (2 mg/kg). 5. These results indicate that this model may be useful for estimating the effects of drugs in the treatment of Parkinson's disease.

DOI： 10.1046/j.1440-1681.1999.03051.x

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記述言語：日本語   出版者・発行元：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.48.1052_4

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掲載種別：研究論文（学術雑誌）  

Peritoneal mast cells from Brown-Norway (BN) rats were compared with those from Wistar and Sprague-Dawley (SD) rats.Peritoneal mast cells from BN rats showed the smallest values in number, cell diameter and histamine contents compared with those from Wistar and SD rats.BN rat peritoneal mast cells were more sensitive to compound 48/80 and anti-IgE than were those from Wistar and SD rats, and they showed a higher response to A23187 than did cells from Wistar rats.The histamine release from passively sensitized peritoneal mast cells was weaker in BN rats than was that from Wistar and SD rats. Copyright (C) 1998 Elsevier Science Inc.

DOI： 10.1016/S0306-3623(98)00063-9

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掲載種別：研究論文（学術雑誌）  

Effects of antiallergic drugs on bradykinin-induced histamine release and intracellular Ca2+ release from peritoneal mast cells were studied in rats. Bradykinin caused a concentration-dependent histamine release as well as Ca2+ release from the intracellular Ca store of peritoneal mast cells. Antiallergic drugs used in this study showed an inhibition of not only histamine release but also Ca2+ release. The Ca2+ release from the intracellular Ca store induced by bradykinin was more sensitive to antiallergic drugs than histamine release from mast cells. Mequitazine and terfenadine caused potent inhibitory effects on both responses, whereas effects of ketotifen and cromolyn sodium were relatively weak. In conclusion, histamine release from mast cells and intracellular C2+ release induced by bradykinin were inhibited by antiallergic drugs similar to those induced by substance P and compound 48/80.

DOI： 10.1358/mf.1998.20.6.485708

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掲載種別：研究論文（学術雑誌）  

The effects of histamine H1 receptor antagonists on compound 48/80- induced scratching behavior were studied in mice. Classical histamine H1 receptor antagonists such as diphenhydramine and chlorpheniramine caused a potent depressant effect on compound 48/80-induced scratching behavior. Histamine H1 receptor antagonists having antiallergic activity (an inhibition of mast cell degranulation), such as azelastine and oxatomide and nonsedative histamine H1 receptor antagonists such as terfenadine, epinastine and astemizole, also showed a relatively potent effect. On the other hand, the effects of tranilast and cromolyn sodium-antiallergic drugs without histamine H1 receptor antagonistic activity-were extremely weak. Diazepam had weak or no depressant effects on compound 48/80-induced scratching behavior. These results suggest that inhibition of compound 48/80- induced scratching behavior is mainly due to histamine H1 receptor antagonistic activity and not to the sedative action of the drugs.

DOI： 10.1016/S0014-2999(98)00288-X

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掲載種別：研究論文（学術雑誌）  

We examined the effects of platelet-activating factor (PAF) on β- adrenoceptors and the functional response to isoproterenol in guinea pig parenchymal strips. PAF caused a reduction in the relaxation of guinea pig lung parenchymal strips induced by the β-adrenoceptor agonist, isoproterenol. In addition, PAF decreased the density of β-adrenoceptors in guinea pigs lung without any change in the affinity. Apafant, a potent PAF antagonist, inhibited the above changes, indicating that it inhibited the downregulation of β-adrenoceptors. These findings suggest that apafant may be effective in nonspecific hyperreactivity in asthma.

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掲載種別：研究論文（学術雑誌）  

The influence of bilateral hippocampal lesions on active avoidance response was studied in rats, as well as the effect of intracerebroventricular (i.c.v.) injection of histamine on memory deficits caused by hippocampectomy. Retardation of learning acquisition was produced by lesioning of the bilateral dorsal hippocampus in active avoidance response. Memory retention was also impaired by hippocampectomy. Although locomotor activity and rearing behavior measured open-field test increased after hippocampal lesions, there was no relation between impairment of learning and increase in exploratory behavior, l.c.v. injection of histamine and i.p. injection of histidine resulted in an improvement of memory deficits (not only learning acquisition but also memory retrieval) induced by hippocampal lesions in rats. Histamine contents of the hippocampus and hypothalamus decreased after hippocampectomy, and a decrease in histamine contents of both areas was restored by histamine (i.c.v.) and histidine (i.p.) injection. In addition, a close relationship was found between decrease in response latency of avoidance response and an increase in histamine content of the hippocampus and hypothalamus after histamine injection.

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掲載種別：研究論文（学術雑誌）  

The effects of histamine and its related compounds on impairment of the passive avoidance response induced by hippocampal lesions were studied in rats. A remarkable impairment of passive avoidance response was observed by bilateral dorsal hippocampal lesions. Intracerebroventricular injection of histamine and intraperitoneal injection of histidine improved the impairment of passive avoidance response in hippocampus-lesioned rats. An ameliorating effect of histamine on memory impairment was mediated via H1-receptors. H1- agonists, 2-thiazolylethylamine and 2-pyridylethylamine, caused the same effect as histamine, whereas H2-agonists, 4-methylhistamine and dimaprit, failed to improve the impairment of passive avoidance response. Pretreatment with H1-antagonists, diphenhydramine and chlorpheniramine, abolished the ameliorating effect of histamine on memory impairment, but H2-antagonists, cimetidine and ranitidine, caused no obvious effect. H3-antagonists, thioperamide and clobenpropit, also improved the memory impairment same as histamine. This effect was blocked by H3-agonist, (R)-α-methylhistamine and H1-antagonist, diphenhydramine, but not by H2-antagonist, cimetidine. Based on these findings, histamine improves the impairment of passive avoidance response induced by hippocampal lesions via H1-receptor. Presynaptic H3- receptor is also involved in modulation of the memory paradigm.

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掲載種別：研究論文（学術雑誌）  

Intraperitoneal injection of endotoxin resulted in bronchial hyperreactivity to histamine in guinea pigs. In addition, endotoxin (lipopolysaccharide, LPS) caused a decrease in the relaxation of the lung parenchymal strips induced by the β-adrenoceptor agonist, isoproterenol (isoprenaline), and a reduction in the number of β-adrenergic binding sites in the lung membrane preparation in guinea pigs. Apafant (CAS 105219-56-5, WEB 2086) was effective in the prevention of endotoxin-induced changes, i.e., bronchial hyperreactivity to histamine, a decrease in the relaxation of lung parenchymal strips induced by isoproterenol and a reduction in the number of β-adrenergic binding sites in the lung membrane preparation in guinea pigs. Ketotifen and ozagrel also prevented the bronchial hyperresponsiveness and endotoxin-induced deterioration of the β-adrenergic system. No remarkable effect was observed with cromolyn sodium and salbutamol in the bronchial hyperreactivity to histamine induced by endotoxin in guinea pigs. Cromolyn sodium also caused no influence on the down-regulation of β-adrenoceptors.

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掲載種別：研究論文（学術雑誌）  

The role of substance P in experimental allergic conjunctivitis induced by egg albumin was investigated with guinea pigs. Increase in vascular permeability of the conjunctiva induced by antigen was significantly inhibited after repeated application of capsaicin. Substance P contents in the conjunctiva of guinea pig were decreased by topical instillation of antigen to the eyes, suggesting that substance P was released from the conjunctiva due to antigen-antibody reaction. Moreover, subconjunctival injection of substance P resulted in a dose-related conjunctivitis, and vascular permeability in the conjunctiva was also increased by substance P. In substance P-induced conjunctivitis, a significant edema was observed in the bulbar and palpebral conjunctiva, but no hyperemia was noted in all instances. Histamine contents of the conjunctiva and tears were not influenced by subconjunctival injection of substance P. However, topical application of antigen and subconjunctival injection of compound 48/80 caused a significant decrease in histamine content, and content of tear was increased by both treatments. An increase in vascular permeability induced by antigen application was significantly inhibited by intravenous injection of FK-888, which is a specific and potent NK1 receptor antagonist. From these results, it is suggested that substance P is responsible for allergic conjunctivitis to some extent, and the conjunctival hyperpermeability induced by substance P occurs through NK1 receptor on the blood vessels, rather than by the direct action on the conjunctival mast cells during allergic conjunctival reactions.

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掲載種別：研究論文（学術雑誌）  

Bradykinin at concentrations higher than 2 μM caused a significant histamine release from rat peritoneal mast cells when extracellular Ca2+ was removed from the medium. Under the same experimental conditions, bradykinin increased Ca2+ release from the intracellular Ca store of the rat peritoneal mast cells, and a clear relationship was observed between the magnitude of histamine release and an increase in fluorescence intensity. Addition of Ca2+ to the medium resulted in an inhibition of the response to bradykinin in a concentration-dependent manner. Almost the same results were obtained when Mg2+, Ba2+ and La3+ were added to the medium. Neither B1 nor B2 antagonists caused significant antagonistic effects on histamine release induced by bradykinin. However, B2 antagonists caused a histamine release of the same potency as bradykinin when applied alone. These results indicate that bradykinin-induced histamine release is not attributable to a bradykinin receptor.

DOI： 10.1248/bpb.19.237

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掲載種別：研究論文（学術雑誌）  

Effects of histamine and related compounds on the bovine iris dilator were investigated. Histamine caused a concentration- related contraction of the bovine iris dilator and IC50 was 1.57 x 10-7 M. The potency of histamine on the bovine iris dilator was almost the same as that observed in guinea pig ileum. Histamine- induced contraction of the bovine iris dilator was antagonized by the H1 antagonists pyrilamine, diphenhydramine and chlorpheniramine, whereas pretreatment with the H2 antagonists cimetidine and ranitidine was not effective. In addition, histamine and the H1 agonist 2-methylhistamine caused a contraction of bovine iris dilator, but the H2 agonist 4-methylhistamine was not effective. An H3 antagonist, thioeramide, also had no contractive effects on the bovine iris dilator. The bovine iris dilator contained a considerable amount of histamine, which was not released by compound 48/80, substance P or by increasing K+ concentration in the medium. In conclusion, histamine caused a potent contraction of the bovine iris dilator via H1 receptor, and this muscle showed a high sensitivity to histamine similar to guinea pig ileum.

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掲載種別：研究論文（学術雑誌）  

Loratadine caused an inhibition of histamine release from rat peritoneal mast culls induced by passively sensitized mast cells, and IC 50 was 9.57 μM. SCH 34117, a metabolite of loratadine, also inhibited histamine release from mast cells, and its potency was more than that of loratadine. Moreover, in ex vivo experiments, loratadine (5 mg/kg, p.o.) as well as terfenadine provided a relatively potent inhibitory effect on histamine release from lung pieces of actively sensitized guinea pigs exposed to antigen.

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掲載種別：研究論文（学術雑誌）  

Epileptogenic activity induced by combined treatment with antiinflammatory drugs and enoxacin was investigated in chronic electrode-implanted rats. Ferubinac ethyl and aspirin DL-lysine showed a spike or spike and wave complex in EEG without showing remarkable behavioral changes when they were injected intraventricularly, although a relatively high dose was needed. Enoxacin, on the other hand, elicited potent epileptogenic activity characterized by uninterrupted high voltage spike and wave complex at doses of 50 and 100 μg. At the same time, rats showed hyperactivity, jumping and violent convulsion. Combined treatment with enoxacin (p.o.) and ferubinac ethyl (i.v.) caused potent epileptogenic activity characterized by uninterrupted burst of high voltage spike and wave complex. Behaviorally, animals showed forelimb clonus, head nodding and generalized convulsion. High voltage spike and wave complex was also observed afer combined treatment with enoxacin (i. vent.) and ferubinac ethyl (i.v. or i. vent.) in association with hyperactivity and jumping and violent convulsion. Nicardipine remarkably inhibited epileptic seizures induced by combined treatment with enoxacin (p.o.) and ferubinac ethyl (i.v.). It is concluded that simultaneous treatment with enoxacin and ferubinac ethyl produced epileptogenic activity when injected intraventricularly, and nicardipine inhibited convulsions induced by combined use of enoxacin (p.o.) and ferubinac ethyl (i.v.).

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掲載種別：研究論文（学術雑誌）  

The effect of mometasone furoate, beclomethasone dipropionate and fluticasone propionate on experimental allergic rhinitis in rats was studied. These drugs caused inhibition on the dye leakage into the nasal cavity induced by antigen in actively sensitized rats. The relative potency of mometasone furoate was 4.13 against beclomethasone dipropionate.

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掲載種別：研究論文（学術雑誌）  

The effect of KW-4679 ((Z)-11-[3-(dimethylamino)propylidene)-6,11-dihydrodibenz[b,e]oxepin-2 -acetic acid hydrochloride, CAS 140462-76-6; proposed INN: olopatadine) on experimental conjunctivitis and rhinitis was studied in comparison with that of ketotifen (CAS 34580-14-8) using guinea pigs and rats, respectively. KW-4679 was effective in inhibiting the antigen- and histamine-induced conjunctivitis by both oral and topical administrations. These effects of KW-4679 were somewhat more potent than those of ketotifen. KW-4679 as well as ketotifen was more effective in inhibiting the histamine-induced conjunctivitis than that seen in antigen-induced conjunctivitis when they were given topically. KW-4679 inhibited the increased dye leakage into the nasal cavity induced not only by antigen in actively sensitized rats but also by histamine perfusion in non-sensitized rats by oral and topical administrations. Similar to ketotifen, the effect of KW-4679 on histamine-induced increase in dye leakage was almost same as that induced by antigen. The potency of KW-4679 was higher than that of ketotifen in the increased dye leakage induced by both antigen and histamine perfusion.

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掲載種別：研究論文（学術雑誌）  

Effects of intracerebroventricular injection of histamine and its related compounds on rectal temperature were studied in mice. Histamine (0.1-1.0 μg) and histidine (500-1,000 mg/kg) caused a dose-related hypothermia. H1 agonist, 2-methylhistamine and 2-thiazolylethylamine also displayed a dose-dependent hypothermia. In addition, H2 agonists, 4-methylhistamine and dimaprit elicited a decrease in body temperature. Preinjection of not only H1-antagonists (diphenhydramine and chlorpheniramine) but also H2 antagonists (cimetidine and ranitidine) abolished histamine-induced hypothermia. Either intracerebroventricular or intraperitoneal injection of thioperamide, a histamine H3 antagonist, showed hypothermia. The hypothermic effect produced by intracerebroventricular injection of thioperamide was significantly blocked by (R)-α-methylhistamine, a selective H3 agonist. In addition, the effect induced by thioperamide was inhibited by H1 and H2 antagonists, indicating that the H3 receptor also participates in histamine-induced hypothermia.

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記述言語：日本語   出版者・発行元：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.44.914_2

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掲載種別：研究論文（学術雑誌）  

Effects of ions on histamine (Hi)-induced depolarization were studied in guinea pig adipocytes. Depolarization induced by Hi in guinea pig adipocytes was decreased by removal of K from the medium or pretreatment with ouabain at concentrations that showed no significant effect themselves. The decrease in membrane potentials induced by Hi was also abolished potently by replacement of Na+ by choline or pretreatment with tetrodotoxin at a concentration that caused no significant action alone. Pretreatment with monensin at a concentration lower than that eliciting the action resulted in a potentiation of Hi-induced depolarization. The depolarization induced by Hi was not affected by the presence of Ca2+ in the medium or pretreatment of the cells by diltiazem. © 1994, The Japanese Pharmacological Society. All rights reserved.

DOI： 10.1254/jjp.66.465

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掲載種別：研究論文（学術雑誌）  

Stimulation of murine peritoneal mast cells with compound 48/80 at a concentration of 1 ug/ml elicited rather slow histamine release; the onset of release was observed 5 s after stimulation, and it reached a plateau at about 60 s. Both inositol-1, 4, 5-trisphosphate (IP3) and inositol-1, 4s-bisphosphate (IP2) contents increased to their maximum 5 s after stimulation. The IP3 content decreased to the control level more rapidly than that of IP2. Changes in the intracellular Ca2+ concentration of the quin 2 loaded mast cells were determined using a video-intensified microscopy system. The fluorescence intensity due to Ca-quin 2 complex increased rapidly after 48/80 stimulation in a Ca-free medium and reached the maximum at about 6-7 s. It became clear that the increase in IP3 content and the resulting Ca2+ release from the intracellular Ca store precede histamine release from murine mast cells. © 1990 S. Karger AG, Basel.

DOI： 10.1159/000235118

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掲載種別：研究論文（学術雑誌）  

The maturational changes in the degree of homologous passive cutaneous anaphylaxis (PCA) and the histamine release from peritoneal mast cells induced by several secretagogues were studied using Wistar rats (4-40 weeks old). Although the increase in vascular permeability of the rat skin induced by intradermal injection of histamine did not change significantly from one maturation period to the next, 6- to 8-weeks old rats were both the most susceptible to PCA reactions and the most responsive to histamine-releasing stimuli. Among rats in this age group (6-8 weeks), the fluidity of the resting cell membrane and the extent of membrane fluidity increase in response to compound 48/80 were greatest. Analysis of the lipid composition of mast cells indicated that the ratio of cholesterol to phospholipids was lowest at the age of 6-8 weeks. From the present study, we concluded that the maturational changes in the extent of histamine release seem to be related to membrane fluidity, which has a profile similar to that of maturation.

DOI： 10.1159/000138537

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掲載種別：研究論文（学術雑誌）  

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掲載種別：研究論文（学術雑誌）  

The effects of cephem antibiotics and their related compounds on aldehyde dehydrogenase obtained from rat liver mitochondria were studied. A pH of 8.8 and reaction temperature 24° were the conditions for measurement of enzyme activity. The apparent Michaelis constant Km values for NAD, acetaldehyde and propionaldehyde were 3.8 × 10-5 M, 4.0 × 10-5 M and 2.5 × 10-5 M, respectively. Cefamandole, cefoperazone and cefmetazole, having a 1-methyl-5-thiotetrazol group at position 3 of the cephem ring, caused a relatively potent inhibition of aldehyde dehydrogenase. Cefmetazole and cefoperazone also showed a significant inhibition on highly purified yeast aldehyde dehydrogenase; the extent of inhibition on yeast enzyme was almost the same as that on rat mitochondrial aldehyde dehydrogenase. The decrease in enzyme activity effected by 1-methyl-1H-tetrazol-5-thiol (MTT) was greater than those of 1H-tetrazol (TZ), 1H-tetrazol-5-thiol and 1-(2-dimethylaminoethyl)-1H-tetrazol-5-thiol, but was, of course, less than that of disulfiram. Cefamandole, cefmetazole and MTT showed competitive inhibition with NAD, while TZ was uncompetitive inhibitor with respect to both NAD and acetaldehyde. Enzyme inhibition caused by disulfiram, cefmetazole and MIT increased timedependently and the addition of 2-mercaptoethanol into the medium effectively and completely restored enzyme inhibition. These results suggest that thiol group at position 5 of 1H-tetrazol ring is responsible for the type of inhibition with NAD, and methyl group at position 1 of 1H-tetrazol ring is important to exhibit a potent inhibition on aldehyde dehydrogenase. © 1987.

DOI： 10.1016/0006-2952(87)90491-6

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掲載種別：研究論文（学術雑誌）  

The hypotensive effects of nisoldipine (Bay k 5552), compared with those of nifedipine, nicardipine and hydralazine, in normotensive rats (NR), spontaneously hypertensive rats (SHR), DOCA-NaCl hypertensive rats (DNR) and renal hypertensive rats (RHR), were studied. The changes in plasma renin activity (PRA) after treatment with nisoldipine and these reference drugs were also studied. The results of this study revealed that: 1. Nisoldipine caused more potent antihypertensive effects in SHR, DNR and RHR than in NR. 2. The antihypertensive effects of nisoldipine in SHR were almost equipotent to those of nifedipine, nicardipine and hydralazine. However, in NR, DNR and RHR, the effects of nisoldipine were weaker than those of the reference drugs. 3. The positive chronotropic effects of nisoldipine were less remarkable than those elicited by nifedipine, nicardipine and hydralazine in all types of hypertensive rats, except SHR. 4. As did nifedipine and nicardipine, nisoldipine caused an increase of the plasma renin activity in NR and SHR, though its potency was weaker than those of nifedipine and nicardipine.

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掲載種別：研究論文（学術雑誌）  

The effects of various cephem antibiotics and related compounds on ethanol metabolism were studied in association with their chemical structures. In rats, cefoperazone, cefbuperazone, cefamandole, latamoxef, cefmetazole, cefotetan, cefmenoxime and cefminox which have the [(1‐methyl‐1H‐tetrazol‐5‐yl) thio] methyl group at position 3 of the cephem ring caused a significant increase in the blood acetaldehyde concentration. In the last three compounds, disulfiram‐like activity was less potent than that evaluated in the preceding compounds. Cefazolin and ceftezole having a 1H‐tetrazol group at position 7 also showed a disulfiram‐like activity. A single administration of 1H‐tetrazol also increased the blood acetaldehyde concentration. Both blood ethanol and acetaldehyde values were increased significantly on administration of these drugs. In beagle dogs, cefoperazone induced a less remarkable but much more sustained increase in the blood acetaldehyde. These results indicate that the 1H‐tetrazol group, as well as the [(1‐methyl‐1H‐tetrazol‐5‐yl) thio] methyl group, is responsible for inducing a disulfiram‐like action and that there is a difference in the potency of the disulfiram‐like activity among the drugs having a [(1‐methyl‐1H‐tetrazol‐5‐yl)thio] methyl group at position 3 of the cephem ring in relation to those in which the side chain is substituted at position 7. Copyright © 1986, Wiley Blackwell. All rights reserved

DOI： 10.1111/j.2042-7158.1986.tb04502.x

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記述言語：日本語   出版者・発行元：(公社)日本栄養・食糧学会  

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記述言語：日本語   出版者・発行元：メディカル葵出版  

本研究では、アレルギー性結膜炎における脂質メディエーター関連化合物の効果について検討した。まず、マウスにくり返し抗原(卵白アルブミン)を点眼投与することにより眼部引っ掻き行動の増加およびアレルギー症状が認められるアレルギー性結膜炎モデルを作製した。作製したモデルを用いて、H1受容体拮抗薬てあるセチリジン、シクロオキシゲナーゼ(COX)-2選択的阻害薬であるエトドラクおよび5-リポキシゲナーゼ阻害薬であるAA-861の効果を検討した。その結果、セチリジンおよびエトドラクの投与により、抗原誘発眼部引っ掻き行動が有意に抑制された。また、セチリジンおよびAA-861の投与により、抗原誘発アレルギー症状が有意に抑制された。以上の成績から、アレルギー性結膜炎の痒みにはH1受容体拮抗薬およびCOX-2選択的阻害薬、アレルギー症状にはH1受容体拮抗薬および5-リポキシゲナーゼ阻害薬が有効であることが示唆された。(著者抄録)

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：JAPANESE PHARMACOLOGICAL SOC  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：JAPANESE PHARMACOLOGICAL SOC  

Web of Science

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：JAPANESE PHARMACOLOGICAL SOC  

Web of Science

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記述言語：日本語   出版者・発行元：(公社)日本薬理学会  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：日本語   出版者・発行元：(株)メディカル葵出版  

ラットを用い,ヒスタミン誘発結膜炎,およびアレルギー性結膜炎に対する塩酸レボカバスチンの効果を,フマル酸ケトチフェンと比較検討した.ヒスタミン誘発結膜炎に対して塩酸レボカバスチンは,フマル酸ケトチフェンと比べ,強力,かつ持続的な結膜炎症状抑制効果を示した.アレルギー性結膜炎に対しても同様の成績が得られ,アレルギー性結膜炎モデルを用いた塩酸レボカバスチンとペミロラストカリウムとの併用効果は塩酸レボカバスチン単独投与,およびペミロラストカリウム単独投与と比べ,有意な結膜炎症状抑制効果を認めた.アレルギー性結膜炎の治療において塩酸レボカバスチンはフマル酸ケトチフェンよりも有用であると考えられ,また,塩酸レボカバスチンとペミロラストカリウムとの併用により,アレルギー性結膜炎に対するより強力な治療効果が得られる可能性が示唆された

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)メディカル葵出版  

ラットを用い,ヒスタミン誘発結膜炎,およびアレルギー性結膜炎に対する塩酸レボカバスチンの効果を,フマル酸ケトチフェンと比較検討した.ヒスタミン誘発結膜炎に対して塩酸レボカバスチンは,フマル酸ケトチフェンと比べ,強力,かつ持続的な結膜炎症状抑制効果を示した.アレルギー性結膜炎に対しても同様の成績が得られ,アレルギー性結膜炎モデルを用いた塩酸レボカバスチンとペミロラストカリウムとの併用効果は塩酸レボカバスチン単独投与,およびペミロラストカリウム単独投与と比べ,有意な結膜炎症状抑制効果を認めた.アレルギー性結膜炎の治療において塩酸レボカバスチンはフマル酸ケトチフェンよりも有用であると考えられ,また,塩酸レボカバスチンとペミロラストカリウムとの併用により,アレルギー性結膜炎に対するより強力な治療効果が得られる可能性が示唆された

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

J-GLOBAL

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2002&ichushi_jid=J00009&link_issn=&doc_id=20021111060719&doc_link_id=%2Fcw4aller%2F2002%2Ft05109%2F253%2F1039-1039%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw4aller%2F2002%2Ft05109%2F253%2F1039-1039%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：JAPANESE PHARMACOLOGICAL SOC  

Web of Science

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2001&ichushi_jid=J00009&link_issn=&doc_id=20011004090234&doc_link_id=%2Fcw4aller%2F2001%2Fs05009%2F030%2F0930-0930%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw4aller%2F2001%2Fs05009%2F030%2F0930-0930%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(公社)日本薬理学会  

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記述言語：日本語   出版者・発行元：(公社)日本薬理学会  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

Brown-Norway(BN)系ラットを用いた抗原抗体反応誘発大腸炎モデルにおける肥満細胞の関与を明らかにする目的で,大腸組織の粘膜障害及びヒスタミン含量の変動に対する能動感作期間の影響を検討した.その結果,抗原物質による大腸粘膜の組織傷害が感作期間に依存して増強され,肥満細胞を介した抗原抗体反応が粘膜障害の発症及び進展に関与していた.又,大腸粘膜組織障害と同時に消化管組織ヒスタミン含量の減少が起きた

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記述言語：日本語   出版者・発行元：(公社)日本薬理学会  

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記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

Brown-Norway(BN)系ラットを用いた抗原抗体反応誘発大腸炎モデルにおける肥満細胞の関与を明らかにする目的で,大腸組織の粘膜障害及びヒスタミン含量の変動に対する能動感作期間の影響を検討した.その結果,抗原物質による大腸粘膜の組織傷害が感作期間に依存して増強され,肥満細胞を介した抗原抗体反応が粘膜障害の発症及び進展に関与していた.又,大腸粘膜組織障害と同時に消化管組織ヒスタミン含量の減少が起きた

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(公社)日本薬理学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2000&ichushi_jid=J00009&link_issn=&doc_id=20001024340622&doc_link_id=%2Fcw4aller%2F2000%2Ft04909%2F203%2F1005-1005%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw4aller%2F2000%2Ft04909%2F203%2F1005-1005%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(公社)日本薬理学会  

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記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

Brown-Norway(BN)系ラットの即時型アレルギー反応による炎症性腸疾患モデルとしての有用性を検討するため,dextran sulfate sodium(DSS)投与による大腸炎モデルおよび抗原抗体反応誘発大腸炎モデルを作製し,Sprague-Dawley(SD)系ラットの成績と比較した.その結果,BN系ラットはDSS大腸炎および抗原抗体反応誘発大腸炎に対して,SD系ラットよりも高い感受性を有することが判明し,潰瘍性大腸炎を始めとする炎症性腸疾患モデル作製におけるBN系ラットの有用性が示唆された.また,大腸粘膜組織障害が誘発されたBN系ラットでは,大腸組織中ヒスタミン含量の減少が認められたことから,大腸粘膜組織障害形成段階において肥満細胞から遊離されたヒスタミンが重要な役割を果たしていると考えられた

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記述言語：日本語   出版者・発行元：(公社)日本薬理学会  

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J-GLOBAL

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記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

Brown-Norway(BN)系ラットの即時型アレルギー反応による炎症性腸疾患モデルとしての有用性を検討するため,dextran sulfate sodium(DSS)投与による大腸炎モデルおよび抗原抗体反応誘発大腸炎モデルを作製し,Sprague-Dawley(SD)系ラットの成績と比較した.その結果,BN系ラットはDSS大腸炎および抗原抗体反応誘発大腸炎に対して,SD系ラットよりも高い感受性を有することが判明し,潰瘍性大腸炎を始めとする炎症性腸疾患モデル作製におけるBN系ラットの有用性が示唆された.また,大腸粘膜組織障害が誘発されたBN系ラットでは,大腸組織中ヒスタミン含量の減少が認められたことから,大腸粘膜組織障害形成段階において肥満細胞から遊離されたヒスタミンが重要な役割を果たしていると考えられた

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(公社)日本薬理学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(公社)日本薬理学会  

J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：(公社)日本薬理学会  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=1999&ichushi_jid=J00009&link_issn=&doc_id=19991029110333&doc_link_id=%2Fcw4aller%2F1999%2F004808%2F351%2F0995-0995%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw4aller%2F1999%2F004808%2F351%2F0995-0995%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

H1-遮断薬ジフェンヒドラミンが睡眠導入薬として使用可能か否かを明らかにする目的で行われた.睡眠の判定にはラット前頭葉皮質脳波のデルタ波(0〜4Hz)のパワースペクトル値を用いて行った.ジフェンヒドラミンは2〜20mg/kgの経口投与で用量依存的に睡眠に至る迄の潜時を短縮し,睡眠持続時間を延長した.有意な効果はジフェンヒドラミンの10mg/kgもしくはそれ以上で観察された.これらの効果はクロルフェニラミンとほぼ同程度であったが,ブロチゾラムよりは弱かった.以上より,ジフェンヒドラミンは,軽度の不眠症の治療に使用可能であると思われる

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=1999&ichushi_jid=J01471&link_issn=&doc_id=19990602070002&doc_link_id=%2Fai6yrtyb%2F1999%2F002705%2F002%2F0777-0781%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai6yrtyb%2F1999%2F002705%2F002%2F0777-0781%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

高いIgE抗体産生能を有するBN系ラットは,能動感作により高い消化管ヒスタミン含量を示す.即時型アレルギー反応の関与する炎症性腸疾患モデルの作製におけるBN系ラットの有用性が示唆された

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記述言語：日本語   出版者・発行元：(公社)日本薬理学会  

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記述言語：日本語   出版者・発行元：(公社)日本薬学会  

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=1998&ichushi_jid=J00009&link_issn=&doc_id=19981111100464&doc_link_id=%2Fcw4aller%2F1998%2Fs04709%2F120%2F1049-1049%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw4aller%2F1998%2Fs04709%2F120%2F1049-1049%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(公社)日本薬理学会  

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記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

雄性ラットではWistar系及びSD系ラットと比較して,BN系ラットは結腸ヒスタミン含有量が高かった.又,雌性BN系ラットでは十二指腸から回腸におけるヒスタミン含有量が高かった.ラットの消化管ヒスタミン含有量には,系統差が存在し,特にBN系ラットでその差が著明である

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記述言語：日本語   出版者・発行元：(公社)日本薬学会  

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記述言語：日本語   出版者・発行元：(公社)日本薬学会  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=1997&ichushi_jid=J00009&link_issn=&doc_id=19970925090521&doc_link_id=%2Fcw4aller%2F1997%2Ft04608%2F061%2F0906-0906%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw4aller%2F1997%2Ft04608%2F061%2F0906-0906%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(公社)日本薬学会  

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記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

抗原抗体反応により生じるラット腹腔肥満細胞からのhistamine遊離に対し,loratadineは濃度依存性の抑制作用を示し,そのIC50は9.57μMであった.loratadineの代謝産物であるSCH34117もIoratadine同様抑制作用を示した.SCH34117の効果はloratadineよりも強力であった.抗原抗体反応により生じるモルモット肺切片からのhistamine遊離に対し,loratadineは5mg/kgの経口投与で有意な抑制作用を示した.terfenadineもloratadineとほぼ同様の効果を示した

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

1)ラット大槽内に投与した際の急性毒性は,イオベルソールの方がイオメプロールよりも低いことが明らかとなった。2)イオベルソールのラットおよびイヌ赤血球に対する影響をその形態および溶血を指標として検討した。イオベルソールの方が鋸歯型赤血球を形成しにくいことが判明し,イヌ赤血球溶血率では高濃度においてイオメプロールに比較的高い傾向がみられた。これらの実験から大槽内毒性試験とオクタノール・水分配係数試験および赤血球における鋸歯型赤血球形成試験は,造影剤の安全性を検討する方法として有用であると考えられた

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=1994&ichushi_jid=J00312&link_issn=&doc_id=19950010170007&doc_link_id=%2Fai6kisoc%2F1994%2F002812%2F007%2F3795-3803%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai6kisoc%2F1994%2F002812%2F007%2F3795-3803%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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記述言語：日本語   出版者・発行元：(公社)日本薬理学会  

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記述言語：日本語   出版者・発行元：(公社)日本薬理学会  

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記述言語：日本語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：JAPANESE PHARMACOLOGICAL SOC  

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