Inhibitory action of peripheral-type benzodiazepines on dopamine release from PC12 pheochromocytoma cells

M. Ohara-Imaizumi, K. Nakazawa, T. Obama, K. Fujimori, A. Takanaka, K. Inoue

研究成果: Contribution to journalArticle査読

23 被引用数 (Scopus)

抄録

Characteristics of the benzodiazepine inhibition of dopamine (DA) release in PC12 cells were investigated. Diazepam inhibited DA release evoked by high concentrations of extracellular. K+ in a dose-dependent manner (IC50, 10 μM). Ro 5-4864 [7-chloro-1,3-dihydro-1-methyl-5-(p-chlorophenyl)-2H-1,4- benzodiazepine-2-one], a peripheral-type benzodiazepine, also inhibited DA release effectively. PK 11195 [1-(2-chlorophenyl)-N-methyl-N-(1- methylpropyl)-3-isoquinoline carboxamide], a benzodiazepine generally considered a peripheral-type benzodiazepine receptor antagonist, did not antagonize the inhibition induced by diazepam, but rather inhibited DA release itself. On the other hand, the central-type benzodiazepines, clonazepam and Ro 15-1788 {ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H- imidazo[1,5a][1,4]benzodiazepine-3-carboxylate} did not affect the DA release. Diazepam, Ro 5-4864 and PK 11195 also inhibited a Ba++-current carried by voltage-gated Ca++ channels, and diazepam suppressed an increase in intracellular Ca++ evoked by 80 mM extracellular K+ as measured by the fura-2 method. These results suggest that the inhibitory action of diazepam and other benzodiazepines on DA release from PC12 cells may be mediated through one type of peripheral-type benzodiazepine receptors which are coupled to voltage-gated Ca++ channels and that these receptors may not necessarily be the same as those in other tissues.

本文言語英語
ページ(範囲)484-489
ページ数6
ジャーナルJournal of Pharmacology and Experimental Therapeutics
259
2
出版ステータス出版済み - 12 1 1991
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子医療
  • 薬理学

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