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

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)484-489
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume259
Issue number2
Publication statusPublished - Dec 1 1991
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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