Gonzalez-Alvear G M, Werling L L
Department of Pharmacology, The George Washington University Medical Center, Washington DC 20037, USA.
Eur J Pharmacol. 1995 Dec 29;294(2-3):713-9. doi: 10.1016/0014-2999(95)00617-6.
The role of the sigma1 receptor in the regulation of N-methyl-D-aspartate (NMDA)-stimulated [3H]dopamine release from rat striatal slices was examined. The sigma receptor agonist 1S,2R-(--)-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)cy clohexylamine (BD737) inhibited stimulated release in a concentration-dependent manner. The sigma1 receptor antagonist, 1-(cyclopropylmethyl)-4-(2'-(4"-fluorophenyl)-2'-oxoethyl)piperidi ne HBr (DuP 734), reversed inhibition of release by BD737. Haloperidol, di-o-tolylguanidine (DTG) and N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (BD1008) reversed the BD737-mediated inhibition of release. Haloperidol and DTG also antagonized inhibition of stimulated release by (+)-pentazocine. Furthermore, BD737 and (+)-pentazocine inhibited stimulated release in the presence of tetrodotoxin, suggesting that sigma1 receptors regulating dopamine release are located on dopaminergic nerve terminals. These data suggest that sigma1 receptors may be important in the regulation of glutamate-stimulated dopamine release.
研究了σ1受体在调节N-甲基-D-天冬氨酸（NMDA）刺激大鼠纹状体切片释放[3H]多巴胺中的作用。σ受体激动剂1S,2R-（-）-N-[2-（3,4-二氯苯基）乙基]-N-甲基-2-（1-吡咯烷基）环己胺（BD737）以浓度依赖的方式抑制刺激释放。σ1受体拮抗剂1-（环丙基甲基）-4-（2'-（4''-氟苯基）-2'-氧代乙基）哌啶HBr（DuP 734）可逆转BD737对释放的抑制作用。氟哌啶醇、二邻甲苯基胍（DTG）和N-[2-（3,4-二氯苯基）乙基]-N-甲基-2-（1-吡咯烷基）乙胺（BD1008）可逆转BD737介导的释放抑制。氟哌啶醇和DTG也可拮抗（+）-喷他佐辛对刺激释放的抑制作用。此外，BD737和（+）-喷他佐辛在存在河豚毒素的情况下抑制刺激释放，这表明调节多巴胺释放的σ1受体位于多巴胺能神经末梢。这些数据表明，σ1受体可能在谷氨酸刺激的多巴胺释放调节中起重要作用。
