| Project/Area Number |
07680843
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Osaka University |
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Principal Investigator |
YAMATODANI Atsushi Osaka Univ., Faculty of Medicine, Professor, 医学部, 教授 (30116123)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Histamine H3-receptors / Presynaptic receptor / Heteroreceptor / GABA transporter / Thioperamide / Microdialysis / Motion sickness / Anesthesia / ヒスタミン / H3-受容体 / 培養神経細胞 / クロベンプロピット / プレシナプス性受容体 / H_3-受容体 / 神経細胞培養 / ニューロケム装置 |
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| Research Abstract |
This project was planned to investigate our hypothesis that the brain histaminergic system plays some of its physiological functions through H3-receptors located on other neuronal systems as heteroreceptor. Using a microdialysis and a Neurochem analysis apparatus, we examined the effects of H3-ligands on the neurotransmitter release. And we found that thioperamide, the most popular H3-antagonist, increased release of GABA form the rat hypothalamus. This increase was Ca2+-independent and H3-agonist could not inhibit the effect. Furthermore, clobenpropit, a more specific H3-antagonist, did not increase GABA release. Thus we concluded that thioperamide increased extracellular concentration of GABA by possibly inhibition of GABA transporter. Thioperamide has been used in many investigations of physiological roles of brain histaminergic system as a pharmacological tool to increase histamine release in the brain. Present result indicates that these previous reports should be reexamined to exclude possible participation of GABA in the results.
Next, we explore the possibility of H3-ligands as some therapeutic drug. By animal experiments using rats, we found that H3-antagonists were effective in prevention of motion sickness. The effect of H3-ligands as supplemental agents of anesthesia was also examined.
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