Waters N, Löfberg L, Svensson K, Carlsson A
Department of Pharmacology, University of Göteberg, Sweden.
Eur J Pharmacol. 1990 Oct 23;187(3):425-34. doi: 10.1016/0014-2999(90)90369-h.
The effects of the preferential autoreceptor antagonist (+)-AJ 76 on dopamine release and metabolism were studied in the brain microdialysis model. The Ca2+ dependence of the effects of (+)-AJ 76 and d-amphetamine were compared. We found that (+)-AJ 76 increased the release and metabolism of dopamine and that the release was saturable. The release of dopamine by (+)-AJ 76 was dependent on extracellular Ca2+. However, the effects of (+)-AJ 76 on dopamine metabolism were independent of extracellular Ca2+. The effects of d-amphetamine on dopamine release and metabolism were independent of Ca2+. We conclude that the dopamine released by (+)-AJ 76 is dependent on neuronal impulse flow and that the dopamine released is of vesicular origin. The effects on dopamine metabolism and release may be exerted via different mechanisms. In contrast, the release and metabolism of dopamine by d-amphetamine were independent of impulse flow and extracellular Ca2+. We suggest that (+)-AJ 76 and d-amphetamine release dopamine from different pools.
在脑微透析模型中研究了选择性自受体拮抗剂(+)-AJ 76对多巴胺释放和代谢的影响。比较了(+)-AJ 76和d-苯丙胺作用的钙依赖性。我们发现(+)-AJ 76增加了多巴胺的释放和代谢，且这种释放是可饱和的。(+)-AJ 76引起的多巴胺释放依赖于细胞外钙。然而，(+)-AJ 76对多巴胺代谢的作用不依赖于细胞外钙。d-苯丙胺对多巴胺释放和代谢的作用不依赖于钙。我们得出结论，(+)-AJ 76释放的多巴胺依赖于神经元冲动流，且释放的多巴胺来源于囊泡。对多巴胺代谢和释放的作用可能通过不同机制发挥。相比之下，d-苯丙胺引起的多巴胺释放和代谢不依赖于冲动流和细胞外钙。我们认为(+)-AJ 76和d-苯丙胺从不同的储存池释放多巴胺。
