Schmidt C J, Lobur A, Lovenberg W
Naunyn Schmiedebergs Arch Pharmacol. 1986 Dec;334(4):377-82. doi: 10.1007/BF00569373.
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.
通过抑制钾离子刺激的预加载大鼠纹状体切片中[3H]多巴胺和[14C]乙酰胆碱的释放，来检测假定的多巴胺自身受体激动剂B-HT 920的突触前选择性。在微摩尔范围内，B-HT 920对20 mM钾离子诱发的两种标记神经递质的释放产生浓度依赖性抑制。B-HT 920对[3H]多巴胺和[14C]乙酰胆碱释放的作用被(+)布他拉莫完全阻断，但不被(-)布他拉莫阻断。选择性D2拮抗剂舒必利同样阻断了B-HT 920对两种标记神经递质释放的抑制作用，表明这两种反应均由D2受体介导。单独使用(+)布他拉莫可提高刺激的[3H]多巴胺释放，提示内源性释放的多巴胺大量占据了自身受体。用妥拉唑啉和α2激动剂B-HT 933进行的实验未表明α-肾上腺素能受体活性参与B-HT 920对任何一种递质释放的抑制作用。释放抑制是B-HT 920的选择性作用，因为该药物对钾离子刺激的[3H]5-羟色胺释放无影响。结果表明，与体内给药后观察到的效应模式相反，体外B-HT 920对突触前和突触后多巴胺受体均有活性。
