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Invited Symposium: Neuronal Histamine Systems and Behavior






Abstract

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Materials & Methods

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Histamine H1 Receptor-Mediated Inhibition of Potassium-evoked Release of 5-Hydroxytryptamine from Mice Brains : A Study of H1 Receptor Knockout Mice

Yanai, K. (Department of Pharmacology I, Tohoku University School of Medicine, Japan)
Son, LZ (Department of Pharmacology I, Tohoku University School of Medicine, Japan)
Mobarakeh, JI (Department of Pharmacology I, Tohoku University School of Medicine, Japan)
Kuramasu, A. (Department of Pharmacology I, Tohoku University School of Medicine, Japan)
Li, ZY (Department of Pharmacology I, Tohoku University School of Medicine, Japan)
Sakurai, E. (Department of Pharmacology I, Tohoku University School of Medicine, Japan)
Hashimoto, Y. (Department of Anesthesiology, Tohoku University School of Medicine, Japan)
Hashimoto, T. (Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Japan)
Watanabe, T. (Department of Pharmacology I, Tohoku University School of Medicine, Japan)

Contact Person: Kazuhiko Yanai (yanai@mail.cc.tohoku.ac.jp)


Abstract

Some antidepressants are most potent competitive histamine H1 anatgonists. It is still unclear whether the H1 antagonism is partly attributed to their antidepressant actions. Brain slices of H1 receptor knockout mice and the wild-type mice were superfused with Ringer bicarbonate solution, and the endogenous release of 5-hydroxytryptamine (5-HT) was measured. The release of 5-HT evoked by 30 mM K+ was significantly decreased in the presence of 10-50 ÁM histamine in the wild-type mice, while that was not inhibited in the mutant mice. H1 receptor-mediated inhibition of serotonin release in the wild-type mice was also observed in the presence of thioperamide. From these data, we postulated that endogenous histamine physiologically inhibits the release of 5-HT through H1 receptors in addition to H3 receptors. The treatment of 2ÁM tetrodotoxin could partly abolish the effects of histamine on the 5-HT release. Bicuculline, a GABA-A antagonist, could reversed the histamine-induced inhibition of 5-HT release in the wild-type mice, suggesting that H1 receptors facilitate the release of GABA, which in turn inhibits 5-HT release. The difference in the effects of d- and l-chlorpheniramine on the 5-HT release in wild-type mice further supports the evidence of the function of H1 receptor modulating 5-HT release.

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Presentation Number SAyanai0260
Keywords: Histamine, H1 receptor, serotonin release, gene targeting, brain slices


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Yanai, K.; Son, LZ; Mobarakeh, JI; Kuramasu, A.; Li, ZY; Sakurai, E.; Hashimoto, Y.; Hashimoto, T.; Watanabe, T.; (1998). Histamine H1 Receptor-Mediated Inhibition of Potassium-evoked Release of 5-Hydroxytryptamine from Mice Brains : A Study of H1 Receptor Knockout Mice. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/huston/yanai0260/index.html
© 1998 Author(s) Hold Copyright