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 language | English |
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Pages (from-to) | 484-489 |
Number of pages | 6 |
Journal | Journal of Pharmacology and Experimental Therapeutics |
Volume | 259 |
Issue number | 2 |
Publication status | Published - Dec 1 1991 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Pharmacology