title: Inhibition of K+-stimulated [3H]dopamine and [14C]acetylcholine release by the putative dopamine autoreceptor agonist, B-HT 920.
abstract: The inhibition of K+-stimulated [3H]dopamine and [14C]acetylcholine release from preloaded rat striatal slices was used to examine the presynaptic selectivity of the putative dopamine autoreceptor agonist, B-HT 920. In the micromolar range, B-HT 920 caused a concentration-dependent inhibition of the release of both labeled neurotransmitters as evoked by 20 mM K+. The effect of B-HT 920 on both [3H]dopamine and [14C]acetylcholine release was completely blocked by (+) butaclamol but not by (-) butaclamol. Sulpiride, a selective D2 antagonist, similarly blocked the inhibitory effect of B-HT 920 on the release of both labeled neurotransmitters indicating both responses were mediated by D2 receptors. (+) Butaclamol alone elevated stimulated [3H]dopamine release suggesting a significant amount of autoreceptor occupancy by endogenously released dopamine. Experiments with tolazoline and the alpha 2 agonist, B-HT 933, did not suggest any involvement of alpha-adrenoceptor activity in the inhibitory effects of B-HT 920 on the release of either transmitter. Inhibition of release was a selective effect of B-HT 920 as the drug was without effect on the K+-stimulated release of [3H]serotonin. The results indicate that in vitro B-HT 920 is active of both pre- and postsynaptic dopamine receptors in contrast to the pattern of effects observed after its in vivo administration.
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002069:Butaclamol / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*
chemical_list: D001381:Azepines; D011954:Receptors, Dopamine; C024763:talipexole; D002069:Butaclamol; D000109:Acetylcholine; D011188:Potassium; D004298:Dopamine