Chang A, Shin S H, Pang S C
Department of Physiology, Queen's University, Kingston, Ontario, Canada.
Endocrine. 1997 Oct;7(2):177-82. doi: 10.1007/BF02778139.
Dopamine is considered to be the major physiological tonic inhibitor of prolactin release, yet there is increasing evidence showing that it can also stimulate prolactin release from lactotrophs. In primary cultured lactotrophs, the major dopamine receptors responsible for inhibiting prolactin release are dopamine D2 receptors. A dopamine receptor subtype may be responsible for the stimulatory action, yet one cannot exclude the possibility that a dopamine D2 receptor can play dual roles. This study was therefore undertaken to investigate if dopamine both stimulates and inhibits prolactin secretion through activation of the same dopamine D2 receptor. GH4ZR7 cells, which have only one type of dopamine receptors--D2s, were perifused with different concentrations of dopamine, and the perifusate was assayed for prolactin; 10(-7) mol/L dopamine stimulated prolactin release (p < 0.05; n = 5), whereas 5 x 10(-4) mol/L dopamine inhibited prolactin secretion (p < 0.05; n = 5). In the pertussis toxin-treated cells, 10(-7) mol/L dopamine stimulated prolactin release (p < 0.05; n = 5), and 5 x 10(-4) mol/L dopamine did not significantly change the rate of prolactin release. These results indicate that both the stimulatory and inhibitory actions of dopamine are likely mediated by the same D2 receptor subtype, since GH4ZR7 cells express only D2s receptors. They also confirm that the inhibitory action of dopamine is mediated through a Gi protein; and the stimulatory action of dopamine is mediated through a PTX-insensitive pathway. These findings suggest that D2 receptors are coupled to both Gi and Gs proteins.
多巴胺被认为是催乳素释放的主要生理性张力抑制剂，但越来越多的证据表明，它也能刺激催乳素细胞释放催乳素。在原代培养的催乳素细胞中，负责抑制催乳素释放的主要多巴胺受体是多巴胺D2受体。一种多巴胺受体亚型可能负责这种刺激作用，但不能排除多巴胺D2受体发挥双重作用的可能性。因此，本研究旨在探讨多巴胺是否通过激活同一多巴胺D2受体来刺激和抑制催乳素分泌。仅表达一种多巴胺受体——D2s的GH4ZR7细胞用不同浓度的多巴胺进行灌流，并检测灌流液中的催乳素；浓度为10(-7)mol/L的多巴胺刺激催乳素释放（p<0.05；n=5），而浓度为5×10(-4)mol/L的多巴胺抑制催乳素分泌（p<0.05；n=5）。在百日咳毒素处理的细胞中，浓度为10(-7)mol/L的多巴胺刺激催乳素释放（p<0.05；n=5），而浓度为5×10(-4)mol/L的多巴胺并未显著改变催乳素释放速率。这些结果表明，多巴胺的刺激和抑制作用可能均由同一D2受体亚型介导，因为GH4ZR7细胞仅表达D2s受体。它们还证实，多巴胺的抑制作用是通过Gi蛋白介导的；多巴胺的刺激作用是通过一条对百日咳毒素不敏感的途径介导的。这些发现提示，D2受体与Gi和Gs蛋白均偶联。
