記述言語：英語  

DOI： 10.1016/j.ejphar.2010.07.039

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記述言語：英語  

DOI： 10.1016/j.intimp.2010.03.007

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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：(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：英語  

DOI： 10.1016/j.ejphar.2009.10.066

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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   出版者・発行元：(公社)日本薬学会  

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記述言語：英語  

DOI： 10.1002/jps.21388

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記述言語：英語  

DOI： 10.1254/jphs.08164FP

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：英語  

DOI： 10.1021/jm701191z

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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：英語  

DOI： 10.1016/j.bmc.2006.10.029

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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  

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記述言語：英語   出版者・発行元：PROUS SCIENCE, SA  

The present study was undertaken to investigate the effect of paroxetine, a selective serotonin reuptake inhibitor (SSRI). on marble-burying behavior in mice in comparison with those of fluvoamine and clomipramine. Marble-burying test is extensively used as an animal model for obsessive/compulsive disorder A significant inhibition in marble-burying behavior was observed with paroxetine, at a dose of,10 mg/kg. The earlier SSRI, fluvoxamine, also significantly inhibited marble-burying behavior at a dose of 30 mg/kg. Although clomipramine. a tricyclic antidepressant, caused an inhibition in marble-burying behavior, a high dose of 100 mg/kg was needed to show a significant effect. On the other hand. all the drugs used in the present study showed no significant changes in spontaneous locomotor activity at doses inhibiting marble-burying behavior. In conclusion, it was confirnied that paroxetine has a potent inhibitory effect on marble-burying behavior in mice, and could have a similar antiobsessive/ anticompulsive activity in hunan beings. (c) 2005 Prous Science. All rights reserved.

DOI： 10.1358/mf.2005.27.10.948883

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記述言語：英語   出版者・発行元：BLACKWELL PUBLISHING LTD  

Background Histamine is one of the most common chemical mediators causing pruritus, and H-1 receptor antagonists have been used as a first choice in its treatment. On the other hand, although the presence of H-3 receptors has been identified in the skin, few studies have investigated the involvement of H-3 receptors on pruritus.
Objective The purpose of this study was to examine whether H-3 receptor agonist or antagonist influences the incidence of scratching behaviour in ICR or mast cell-deficient WBB6F(1)-W/W-V mice.
Methods The mice were given an intradermal injection of H-3 receptor agonist or antagonist into the rostral part of the back, and the occurrence of scratching behaviour at the injected site by the hind paws was counted over 60 min.
Results H-3 receptor antagonists, thioperamide and AQ0145 significantly increased the incidence of scratching behaviour in ICR mice. H-3 receptor agonist, (R)-alpha-methylhistamine, had no effect. On the other hand, (R)-alpha-methylhistamine significantly inhibited thioperamide or AQ0145-induced scratching behaviour. In addition, both thioperamide and AQ0145 elicited scratching behaviour in mast cell-deficient WBB6F(1)-W/W-V mice.
Conclusion From these results, it may be concluded that H-3 receptors are involved in the modulation of pruritus in the skin, and mast cells are not essential in this response. In addition, H-3 receptor agonists can be useful as a novel therapeutic approach against pruritus.

DOI： 10.1111/j.1365-2222.2004.01876.x

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

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 wildtype (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, antagonists diphenhydramine and chlorpheniramine and the NK1 antagonists, L-732,13 8 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. (C) 2003 Published by Elsevier B.V.

DOI： 10.1016/S1567-5769(03)00009-2

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記述言語：英語   出版者・発行元：BLACKWELL PUBLISHING LTD  

Background Although the roles of histamine H-3 receptors have been studied in several tissues such as the brain, lung, spleen, colon and peripheral sensory nerve endings, the involvement of H-3 receptors in skin responses particularly in relation to scratching behaviour are not well documented.
Objectives This work was performed to study the effects of histamine H-3 antagonists on scratching behaviour in mast cell-deficient mice.
Methods Histamine H-3 antagonists iodophenpropit and clobenpropit, histamine and substance P were injected intradermally into the rostral part of the back of mast cell-deficient (WBB6F1 W/W-v ) and wild-type (WBB6F1+/+) mice and scratching behaviour was measured for 60 min. The effects of H-1 antagonists on scratching behaviour induced by H-3 antagonists were also investigated.
Results Intradermal injection of iodophenpropit and clobenpropit at doses of 10 and 100 nmol per site caused significant increases in scratching behaviour in both mast cell-deficient and wild-type mice. Histamine also caused a dose-related increase in the incidence of scratching behaviour, and a significant effect was observed at a dose of 100 nmol per site in both mast cell-deficient and wild-type mice. Substance P was also effective in causing scratching behaviour in both mast cell-deficient and wild-type mice. However, histamine H-1 antagonists diphenhydramine and chlorphenamine failed to inhibit H-3 antagonist-induced scratching behaviour in both types of mice.
Conclusions Our results indicated that intradermal injection of H-3 antagonists induces scratching behaviour and that chemical mediators other than histamine seem to be involved in the response.

DOI： 10.1046/j.1365-2133.2003.05341.x

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

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 (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. (C) 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   出版者・発行元：ELSEVIER SCIENCE BV  

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. (C) 2003 Elsevier Science B.V All rights reserved.

DOI： 10.1016/S0014-2999(03)01786-2

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記述言語：英語   出版者・発行元：PROUS SCIENCE, SA  

The effects of [Arg(8)]-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 hippocamous. The effects of the metabolic fragments AVP4-9 and A VP4-8 on rCBF were relatively weak. OPC-31260, a vasopressin V-2 antagonist, antagonized the AVP-induced increase in rCBF in the hippocampus. Furthermore, subcutaneous injection of DDAVP, a V-2 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 V-1 antagonist. Intracerebroventricular injection of AVP caused no significant changes in rCBF in the hippocampus, even at a dose of 10 ng/site. (C) 2003 Prous Science. All rights reserved.

DOI： 10.1358/mf.2003.25.3.769639

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記述言語：英語   出版者・発行元：ELSEVIER SCI IRELAND LTD  

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 I 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. (C) 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   出版者・発行元：ELSEVIER SCIENCE BV  

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 H 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 H 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. (C) 2003 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S1567-5769(02)00299-0

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

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. (C) 2002 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S0006-8993(02)03012-3

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記述言語：英語   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

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   出版者・発行元：ELSEVIER SCIENCE BV  

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. (C) 2002 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S0014-2999(02)02005-8

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記述言語：英語   出版者・発行元：PROUS SCIENCE, SA  

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. (C) 2002 Prous Science. All rights reserved.

DOI： 10.1358/mf.2002.24.5.802303

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

The role of histamine H-1 receptors in nasal allergic symptoms (sneezing and nasal rubbing) were studied using histamine H-1 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 H-1 receptor-deficient mice. The histamine H-1 receptor agonist 2-pyridylethylamine induced sneezing and nasal rubbing in a dose-dependent manner in wild-type mice, but no such increase was fund in histamine H, receptor-deficient mice. On the other hand, the histamine H-2 receptor agonist dimaprit did not increase sneezing and nasal rubbing in wild-type mice. Histamine H-1 receptor antagonists such as chlorpheniramine and epinastine significantly inhibited nasal allergic symptoms caused by histamine, but the histamine H-2 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 H, receptors play an important role in nasal allergy symptoms induced by histamine. (C) 2002 Elsevier Science B.V All rights reserved.

DOI： 10.1016/S1567-5769(02)00010-3

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記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

We examined the effects of a histidine-deficient diet on brain histamine contents as well as on learning and memory using the eight-ann 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. (C) 2002 Elsevier Science Inc. All rights reserved.

DOI： 10.1016/S0024-3205(02)01504-7

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記述言語：英語   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

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.

DOI： 10.1248/bpb.25.256

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記述言語：英語   出版者・発行元：PROUS SCIENCE, SA  

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. (C) 2002 Prous Science. All rights reserved.

DOI： 10.1358/mf.2002.24.1.677122

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記述言語：英語   出版者・発行元：JAPANESE PHARMACOLOGICAL SOC  

We investigated the effects of histidine on spatial memory deficits induced by the 5-HT1A-receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetratin (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   出版者・発行元：ELSEVIER SCIENCE BV  

The effects of [Arg(8)] vasopressin on histamine H-1 receptor antagonist-induced memory deficits were investigated using the eight-arm radial maize performance test in rats. Pyrilamine and diphenhydramine as well as scopolamine induced memory deficits characterized by increaser in the number of total errors, reference memory errors and working memory errors. [Arg(8)] vasopressin improved not only scopolamine-but also pyrilamine-and diphenhydramine-induced memory deficits, although a high dose of [Arg(8)] vasopressin was needed to antagonize pyrilamine-induced memory deficits. The effects of pyrilamine on the brain [Arg(8)] vasopressin content were studied, and the hippocampus [Arg(8)] vasopressin content was shown to be decreased after pyrilamine injection. From these observations, it seems likely that [Arg(8)] vasopressin participates in not only the cholinergic system but also the histaminergic system in spatial memory. (C) 2001 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S0014-2999(01)01080-9

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記述言語：英語   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

The present study,vas 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 mug/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 mug/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 die 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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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

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. (C) 2000 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S0006-8993(00)03041-9

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

To clarify the role of histamine H-1 receptors in allergic conjunctivitis, changes in vascular permeability of the conjunctiva were measured in histamine H-1 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 H-1 receptor deficient mice. On the other hand, no differences were observed between wild-type and histamine H-1 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 H-1 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 H-1 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 H-1 receptor. (C) 2000 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S0014-2999(00)00863-3

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記述言語：英語   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

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, Le. 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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記述言語：英語   出版者・発行元：JAPANESE PHARMACOLOGICAL SOC  

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 degrees C for 10 min. Histamine contents of the supernatant and cell pellet were measured by an automated fluorometric method. Prostaglandin D-2 (PGD(2)) 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 PGD(2) (1.0 mg/ml) from mast cells, but vancomycin did not affect concanavalin A-induced histamine and PGD(2) release. Teicoplanin (more than 0.07 mg/ml) significantly stimulated histamine and PGD(2) release from mast cells and it also significantly potentiated concanavalin A-induced histamine and PGD:! 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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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

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 H-1-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 H-1-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. (C) 2000 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S0162-3109(00)00173-9

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記述言語：英語   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

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 35 d. 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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記述言語：英語   出版者・発行元：PROUS SCIENCE, SA  

The present study was performed to clarify the mechanism responsible for the drowsiness caused by first generation H-1 antagonists according to electroencephalogram activity. All H-1 antagonists used on the present study caused the EEG-recorded drowsiness pattern, i.e., increases in EEG power spectra of the delta and theta bands at the frontal cortex in rats. The potency of cyproheptadine was greater than those of diphenydramine and promethazine, while that of pyrilamine was less than those of the other drugs examined. The increase in EEG power spectra in the delta band induced by H-1 antagonists was antagonized by pretreatment with both histidine and physostigime. The effect of pyrilamine was more potently antagonized by histidine and less potently antagonized by physostigmine as compared to diphenylhydramine, promethazine and cyproheptadine. The increases in EEG power spectra induced by H-1 antagonists were neither antagonized nor potentiated by 5-hydroxytryptophan. These results clearly indicate that the increases in EEG power spectra in the delta and theta bands at the frontal cortex in rats induced by first generation H-1 antagonists are responsible for both histaminergic and cholingeric mechanisms. (C) 2000 Prous Science. All rights reserved.

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記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

The effects of metabolic fragments of [Arg(8)]-vasopressin (AVP), [pGlu(4), Cyt(6)]AVP (AVP(4-9)), and desglycinamide-[pGlu(4), Cyt(6)]AVP (AVP(4-8)) on the growth of hippocampal neurons in culture were investigated in comparison with those of AVP. AVP(4-9) caused a significant increase in filopodial length following 96 h of exposure at concentrations higher than 300 nM. AVP(4-9) was more potent than AVP. AVP(4-8) also induced an increase in filopodial length, but this effect was less than that of AVP. The selective V-1 agonist [Phe(2), Ile(3), Orn(8)]-vasopressin caused a significant increase in filopodial length, whereas the selective V-2 agonist [deamino-Cys(1), D-Arg(8)]-vasopressin showed no such effect. OPC-21268, a vasopressin V-1 antagonist, blocked AVP and AVP fragment-induced increases in filopodial length. However, the V-2 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 AVP(4-9) and AVP(4-8) increased filopodial length in cultured hippocampal neurons by activating V-1 receptors. Both phenomena induced by AVP(4-9) and AVP(4-8) were associated with intracellular calcium mobilization. (C) 2000 Elsevier Science Inc.

DOI： 10.1016/S0361-9230(99)00249-X

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記述言語：英語   出版者・発行元：JAPANESE PHARMACOLOGICAL SOC  

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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記述言語：英語   出版者・発行元：KARGER  

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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記述言語：英語   出版者・発行元：OKAYAMA UNIV MED SCHOOL  

The effects of levocabastine, a novel histamine H-1-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 C-4 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 E-4 or thromoboxane B-2. From these findings,it was concluded that levocabastine may be useful for relieving the nasal obstruction in allergic rhinitis caused by inhibition of leukotriene C-4 release.

DOI： 10.18926/AMO/31623

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記述言語：英語   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

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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記述言語：英語  

DOI： 10.1016/S0091-3057(99)00128-8

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記述言語：英語   出版者・発行元：PROUS SCIENCE, SA  

The effects of histamine and related compounds on regional cerebral bloodflow (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 H-1 agonist, 2-thiazolylethylamine, but also the H-2 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 H-1 and H-2 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 tm increase in rCBF via both H-1 and H-2 receptors. (C) 1999 Prous Science. All rights reserved.

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記述言語：英語   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

The present study was performed to see if first-generation histamine H-1-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 H-1-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 H-1-antagonists and brotizolam. The order of potency of H-1-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 H-1-antagonists, with 14-18-fold and 4-14-fold greater effects on sleep latency and duration, respectively. These results clearly show that H-1-antagonists are effective in mild to moderate insomnia as sedative-hypnotic drugs.

DOI： 10.1248/bpb.22.1079

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

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 H-1-receptors. (C) 1999 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S0006-8993(99)01739-4

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記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Changes in intracellular Ca2+ concentration ([Ca2+](i)) induced by [Arg(8)]-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 V-1 vasopressin receptor agonist [Phe(2), Ile(3), Orn(8)]-vasopressin also induced a significant increase in [Ca2+](i), whereas the selective V-2 vasopressin receptor agonist [deamino Cys(1), D-Arg(8)]-vasopressin showed no effect. The AVP-induced increase in [Ca2+](i) was inhibited by the selective V-1 vasopressin receptor antagonist d(CH2)(5)[Tyr(2)(Me), Arg(8)]-vasopressin and nonpeptide V, antagonist OPC-21268. On the other hand, no antagonistic effects were observed with the V vasopressin antagonist desglycinamide-[d(CH2)(5), D-Ile(2), Ile(4), Arg(8)]-vasopressin and nonpeptide V-2 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, omega-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 V-1 VP receptors coupled with N-type calcium channels. (C) 1999 Elsevier Science Inc.

DOI： 10.1016/S0361-9230(99)00064-7

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記述言語：英語   出版者・発行元：PROUS SCIENCE, SA  

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 Ige and type IV allergic reactions were inhibited. (C)1999 Prous Science. All rights reserved.

DOI： 10.1358/mf.1999.21.5.541913

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記述言語：英語   出版者・発行元：BLACKWELL SCIENCE ASIA  

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 mu g) 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：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

1. Peritoneal mast cells from Brown-Norway (BN) rats were compared with those from Wistar and Sprague-Dawley (SD) rats.
2. 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.
3. 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.
4. The histamine release from passively sensitized peritoneal mast cells was weaker in BN rats than was that from Wistar and SD rats. (C) 1998 Elsevier Science Inc.

DOI： 10.1016/S0306-3623(98)00063-9

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記述言語：英語   出版者・発行元：PROUS SCIENCE, SA  

Effects of antiallergic drugs on bradykinin-induced histamine release and intracellular Ca2+ release from peritoneal mast cells were studied ill mrs. 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 tills 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 oil 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. (C) 1998 Prous Science. All rights reserved.

DOI： 10.1358/mf.1998.20.6.485708

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

The effects of histamine H-1 receptor antagonists on compound 48/80-induced scratching behavior were studied in mice. Classical histamine H-1 receptor antagonists such as diphenhydramine and chlorpheniramine caused a potent depressant effect on compound 48/80-induced scratching behavior. Histamine H-1 receptor antagonists having antiallergic activity (an inhibition of mast cell degranulation), such as azelastine and oxatomide and nonsedative histamine H-1 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 H-1 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 H-1 receptor antagonistic activity and not to the sedative action of the drugs. (C) 1998 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S0014-2999(98)00288-X

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記述言語：英語   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

A mouse strain named ASK that was originally isolated from El (epilepsy) mice has been shown to be highly sensitive to anaphylactic shock. Here, we characterized the bases of the sensitivity of ASK mice in comparison with the parental strain, El. More than 90% of ASIC mice, but not El mice that had been sensitized either actively or passively, died within 1 h following an antigen challenge. The anaphylactic death was effectively blocked by diphenhydramine. Plasma histamine levels increased by 30-50 fold in ASK after the antigen challenge, but only a 2-3-fold increase was observed in El mice. All (ElxASK) F-1 mice, either male or female, showed an ASK-like phenotype, suggesting that the impaired plasma histamine response in El mice is due to some recessive mutation(s). Consistent with the plasma histamine responses. cultured mast cells derived from EI bone marrow showed impaired potency to degranulate in response to surface IgE engagement, in contrast to ASK mast cells which undergo normal degranulation. Another characteristic feature of ASK mice is their sensitivity to histamine, since 75% of the mice were killed by the subcutaneous administration of 100-200 mg/kg histamine, while C3H and BALB/c mice were resistant to even 600 mg/kg histamine. Taken together, the major bases of the susceptibility to anaphylactic shock in ASK mice are thought to be the enhanced sensitivity to histamine and the recovered degranulation machinery in mast cells that is impaired in El mice.

DOI： 10.1248/bpb.21.219

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記述言語：英語   出版者・発行元：PROUS SCIENCE, SA  

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 repealed application of capsaicin. Substance P contents in rite conjunctiva of guinea pig were decreased by typical instillation of antigen to rite eyes, suggesting that substance P was released from the conjunctiva due to antigen-antibody reaction. Moreover subconjunctival injection of substance P resulted in a close-related conjunctivitis, and vascular permeability iii the conjunctiva was also increased by substance P. In substance P-induced conjunctivitis, a significant edema was observed in the bulbar and palpebral conjunctiva, bur no hyperemia was noted in all instances. Histamine contents of the conjunctiva and tears were nor 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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記述言語：英語  

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記述言語：英語   出版者・発行元：ECV-EDITIO CANTOR VERLAG MEDIZIN NATURWISSENSCHAFTEN  

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 beta-adrenoceptor agonist, isoproterenol (isoprenaline), and a reduction in the number of beta-adrenergic binding sites in the lung membrane preparation in guinea pigs. Apafant (GAS 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 beta-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 beta-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 beta-adrenoceptors.

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記述言語：英語   出版者・発行元：J R PROUS SA  

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 the bilateral dorsal hippocampus in active avoidance response. Memory retention was also impaired by hippocampectomy. Although locomotor activity and rearing behavior measured by open-field test increased after hippocampal lesions, there was no relation between impairment of learning and increase in exploratory behavior. I.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 mrs. 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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記述言語：英語   出版者・発行元：J R PROUS SA  

Epileptogenic activity induced by combined treatment with antiinflammatory drugs and enoxacin was investigated in chronic electrode-implanted rats. Ferubinac ethyl adn 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 mu g. 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 after 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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記述言語：英語   出版者・発行元：J R PROUS SA  

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 H-1 antagonists pyrilamine, diphenhydramine and chlorpheniramine, whereas pretreatment with the H-2 antagonists cimetidine and ranitidine was not effective. In addition, histamine, and the H-1 agonist 2-methylhistamine caused a contraction of bovine iris dilator; but the H-2 agonist 4-methylhistamine was not effective. An H-3 antagonist, thioperamide, 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 H-1 receptor, and this muscle showed a high sensitivity to histamine similar to guinea pig ileum.

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記述言語：英語   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

Bradykinin at concentrations higher than 2 mu M caused a significant histamine release from rat peritoneal mast cells when estracellular 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 B-1 nor B-2 antagonists caused significant antagonistic effects on histamine release induced by bradykinin. However, B-2 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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記述言語：英語   出版者・発行元：J R PROUS SA  

Effects of intracerebroventricular injection of histamine and its related compounds on rectal temperature were studied in mice. Histamine (0.0-1.0 mu g) and histidine (500-1,000 mg/kg) caused a dose-related hypothermia. H-1 agonist, 2-methylhistamine and 2-thiazolylethylamine also displayed a dose-dependent hypothermia. In addition, H-2 agonists, 4-methylhistamine and dimaprit elicited a decrease in body temperature. Preinjection of not only H-1-antagonists (diphenhydramine and chlorpheniramine) but also H-2 antagonists (cimetidine and ranitidine) abolished histamine-induced hypothermia. Either intracerebroventricular or intraperitoneal injection of thioperamide, a histamine H-3 antagonist, showed hypothermia. The hypothermic effect produced by intracerebroventricular injection of thioperamide was significantly blocked by (R)-a-methylhistamine, a selective H-3 agonist. In addition, the effect induced by thioperamide was inhibited by H-1 and H-2 antagonists, indicating that the H-3 receptor also participates in histamine-induced hypothermia.

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記述言語：英語   出版者・発行元：ECV-EDITIO CANTOR VERLAG MEDIZIN NATURWISSENSCHAFTEN  

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 moi e 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 mts 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 ina eased dye leakage induced by both antigen and histamine perfusion.

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記述言語：英語   出版者・発行元：JAPANESE PHARMACOLOGICAL SOC  

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.

DOI： 10.1254/jjp.66.465

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記述言語：英語   掲載種別：記事・総説・解説・論説等（学術雑誌）   出版者・発行元：KARGER  

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記述言語：英語   出版者・発行元：KARGER  

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記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

DOI： 10.1016/0006-2952(87)90491-6

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記述言語：英語   出版者・発行元：ECV-EDITIO CANTOR VERLAG MEDIZIN NATURWISSENSCHAFTEN  

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記述言語：英語   出版者・発行元：ROYAL PHARMACEUTICAL SOC GREAT BRITAIN  

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

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