Non-Competitive Antagonism by Hirsuteine of Nicotinic Receptor-Mediated Dopamine Release from Rat Pheochromocytoma Cells.
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概要
- 論文の詳細を見る
Effects of hirsuteine, an indole alkaloid extracted from Uncaria genus, on nicotine and high K-induced responses were investigated in rat pheochromocytoma PC12 cells. Hirsuteine (300 nM-10 μM)inhibited dopamine release evoked by 100 μM nicotine in a concentration-dependent manner. Hirsuteine did not produce a parallel shift of the concentration-response relationship curve for nicotine, but reduced maximal dopamine release. Dopamine release evoked by 60 and 155 mM KCl was also inhibited by hirsuteine, but the concentration necessary for significant inhibition was higher (more than 10 μM). Under whole cell voltage-clamp, hirsuteine reversibly inhibited inward currents activated by 100 μM nicotine. The current inhibition was slightly accelerated by hyperpolarization. The results suggest that hirsuteine non-competitively antagonizes nicotine-evoked dopamine release by blocking ion permeation through nicotinic receptor channel complexes. The blockade of Ca channels, which are activated during nicotine-evoked depolarization, may not play a major role in the antagonism.
- 公益社団法人 日本薬理学会の論文
著者
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Nakazawa Ken
Division Of Pharmacology National Institute Of Health Sciences
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INOUE Kazuhide
Division of Biosignaling, National Institute of Health Sciences
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Fujimori Kannosuke
Division of Pharmacology, National Institute of Hygienic Sciences
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Obama Tomoko
Division Of Pharmacology National Institute Of Hygienic Sciences
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Takanaka Akira
Division Of Pharmacology Bsrc National Institute Of Hygienic Sciences
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Fujimori Kannosuke
Division Of Pharmacology National Institute Of Hygienic Sciences
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Watano Tomokazu
Division of Pharmacology, National Institute of Hygienic Sciences
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Mori Mayumi
Division of Pharmacology, National Institute of Hygienic Sciences
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