PT  - JOURNAL ARTICLE
AU  - M Ohara-Imaizumi
AU  - K Nakazawa
AU  - T Obama
AU  - K Fujimori
AU  - A Takanaka
AU  - K Inoue
TI  - Inhibitory action of peripheral-type benzodiazepines on dopamine release from PC12 pheochromocytoma cells.
DP  - 1991 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 484--489
VI  - 259
IP  - 2
4099  - http://jpet.aspetjournals.org/content/259/2/484.short
4100  - http://jpet.aspetjournals.org/content/259/2/484.full
SO  - J Pharmacol Exp Ther1991 Nov 01; 259
AB  - 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 microM). 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-methyl-propyl)-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.