研究者詳細 - 杉本　幸雄

論文 - 杉本　幸雄

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Strain differences in histamine release from peritoneal mast cells in rats

Y. Sugimoto, H. Ohishi, T. Toyota, C. Kamei

General Pharmacology 31 ( 4 ) 613 - 616 1998年10月

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

Effects of antiallergic drugs on histamine release from rat peritoneal mast cells induced by bradykinin

Y. Sugimoto, T. Tarumi, Q. E. Zhao, Y. Fujii, C. Kamei

Methods and Findings in Experimental and Clinical Pharmacology 20 ( 6 ) 457 - 462 1998年7月

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

Effects of histamine H<inf>1</inf> receptor antagonists on compound 48/80-induced scratching behavior in mice

Yukio Sugimoto, Keiko Umakoshi, Nao Nojiri, Chiaki Kamei

European Journal of Pharmacology 351 ( 1 ) 1 - 5 1998年6月

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

Effects of apafant on PAF-induced downregulation of β-adrenoceptors in guinea pigs

Y. Sugimoto, Y. Nakayama, H. Kishida, T. Hayakawa, R. Fujiwara, C. Kamei

Methods and Findings in Experimental and Clinical Pharmacology 19 ( 8 ) 547 - 552 1997年

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.

Effects of intracerebroventricular injection of histamine on memory deficits induced by hippocampal lesions in rats

Chiaki Kamei, Zhong Chen, Satoru Nakamura, Yukio Sugimoto

Methods and Findings in Experimental and Clinical Pharmacology 19 ( 4 ) 253 - 259 1997年

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.

Effects of histamine and its related compounds on impairment of passive avoidance response following hippocampal lesions in rats

Z. Chen, Y. Sugimoto, C. Kamei

Journal of Brain Science 23 ( 2-3 ) 225 - 240 1997年

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.

Effect of apafant on bronchial hyperresponsiveness and down-regulation of β-adrenoceptors induced by endotoxin in guinea pigs

Yukio Sugimoto, Takuma Mihara, Tsuyoshi Hayakawa, Yukinobu Nakayama, Hisako Kishida, Chiaki Kamei

Arzneimittel-Forschung/Drug Research 47 ( 7 ) 837 - 841 1997年

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.

Role of substance P in experimental allergic conjunctivitis in guinea pigs

Masako Yamaji, Miho Takada, Rie Fujiwara, Hiroko Ohishi, Keiji Izushi, Yukio Sugimoto, Chiaki Kamei

Methods and Findings in Experimental and Clinical Pharmacology 19 ( 9 ) 637 - 643 1997年

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.

Mechanism of bradykinin-induced histamine release from rat peritoneal mast cells

Qiu E. Zhao, Takuma Mihara, Yukio Sugimoto, Chiaki Kamei

Biological and Pharmaceutical Bulletin 19 ( 2 ) 237 - 240 1996年2月

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

Effects of histamine and related compounds on the bovine iris dilator

Chiaki Kamei, Yukio Sugimoto, Yasushi Okumura

Methods and Findings in Experimental and Clinical Pharmacology 18 ( 4 ) 273 - 278 1996年

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.

Effect of loratadine on histamine release induced by antigen-antibody reaction

Chiaki Kamei, Yukio Sugimoto, Masako Yamaji, Miho Takada

Japanese Pharmacology and Therapeutics 24 ( 1 ) 49 - 52 1996年

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.

Epileptogenic activity induced by combined treatment with antiinflammatory drugs and enoxacin and its inhibition by a calcium antagonist, nicardipine

Chiaki Kamei, Yukio Sugimoto, Hiroko Ohishi, Yasushi Okumura, Kazuhiro Kitazumi

Methods and Findings in Experimental and Clinical Pharmacology 18 ( 9 ) 579 - 588 1996年

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.).

Effect of mometasone furoate on experimental allergic rhinitis in rats

C. Kamei, Y. Sugimoto, H. Kakinoki, T. Izumo, C. Ichiki

Japanese Pharmacology and Therapeutics 23 ( 11 ) 109 - 112 1995年

Effect of (Z)-11-[3-(dimethylamino)propylidene]-6,11-dihydrodibenz[b,e]oxepin-2- acetic acid hydrochloride on experimental allergic conjunctivitis and rhinitis in rats and guinea pigs

C. Kamei, Y. Sugimoto, S. Nakamura, C. Zhong

Arzneimittel-Forschung/Drug Research 45 ( 9 ) 1005 - 1008 1995年

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.

Effects of intracerebroventricular injection of histamine and its related compounds on rectal temperature in mice

Z. Chen, Y. Sugimoto, C. Kamei

Methods and Findings in Experimental and Clinical Pharmacology 17 ( 10 ) 669 - 675 1995年

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.

62 モルモットの実験的結膜炎の作成および抗アレルギー薬の効果に関する検討

出石啓治, 杉本幸雄, 亀井千晃

アレルギー 44 ( 8 ) 914 - 914 1995年

The Role of Ions on Histamine-Induced Depolarization in Isolated Guinea Pig Adipocytes

Chiaki Kamei, Yukio Sugimoto

The Japanese Journal of Pharmacology 66 ( 4 ) 465 - 469 1994年

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

Sequential analysis of histamine release and intracellular Ca²⁺ release from murine mast cells

Kenji Tasaka, Yukio Sugimoto, Mitsunobu Mio

International Archives of Allergy and Immunology 91 ( 2 ) 211 - 213 1990年

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

Influence of aging on the histamine release and membrane fluidity of rat peritoneal mast cells

M. Mio, H. Akahori, Y. Sugimoto, M. Akagi, K. Tasaka

Pharmacology 38 ( 3 ) 191 - 200 1989年

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

The antihypertensive effect of consecutive administration of nisoldipine in spontaneously hypertensive rats

K. Tasaka, C. Kamei, T. Hokonohara, Y. Sugimoto

Japanese Pharmacology and Therapeutics 17 ( 4 ) 417 - 423 1989年

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