Judd A M, Login I S, Kovacs K, Ross P C, Spangelo B L, Jarvis W D, MacLeod R M
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.
Endocrinology. 1988 Nov;123(5):2341-50. doi: 10.1210/endo-123-5-2341.
Although dopamine inhibits PRL release from the normal anterior pituitary lactotroph, a conclusive demonstration of the mechanisms involved in this response has been impeded by the presence of other cell types in the anterior pituitary. To circumvent this problem, we have isolated a clonal cell line, designated MMQ, from the 7315a rat pituitary tumor. The MMQ cell is an exemplary model for our use because it only secretes PRL. Our studies show that dopamine inhibits secretagogue-induced PRL release from these cells. In addition, dopamine decreases the intracellular cAMP concentration in MMQ cells that have been exposed to forskolin, cholera toxin, or vasoactive intestinal polypeptide, each a stimulator of cAMP generation. This inhibition is, in turn, reversed by the dopamine antagonist haloperidol and by pertussis toxin, an inactivator of the GTP-binding coupling protein. Dopamine also decreases the uptake and fractional efflux of 45Ca2+ by MMQ cells that have been exposed to the calcium channel activator maitotoxin. It seems, therefore, that dopamine decreases PRL release from MMQ cells at least in part by decreasing intracellular cAMP levels and calcium uptake. In additional experiments, we have found that MMQ cells are responsive to somatostatin, estrogen, progesterone, and acetylcholine, but not to TRH, angiotensin II, neurotensin, or bombesin. Furthermore, these cells possess a functional protein kinase-C system, as evidenced by the increase in PRL release and decrease in stimulated intracellular cAMP levels that occur in response to treatment with phorbol diesters. We suggest that the MMQ cell line will prove a useful model system for study of the biochemical effects of dopamine and other factors that modify PRL release.
尽管多巴胺可抑制正常垂体前叶催乳素细胞释放催乳素（PRL），但由于垂体前叶存在其他细胞类型，阻碍了对这一反应所涉及机制的确切论证。为规避这一问题，我们从7315a大鼠垂体肿瘤中分离出了一个克隆细胞系，命名为MMQ。MMQ细胞是我们可用的一个典型模型，因为它只分泌PRL。我们的研究表明，多巴胺可抑制促分泌素诱导的这些细胞释放PRL。此外，多巴胺可降低已暴露于毛喉素、霍乱毒素或血管活性肠肽（均为cAMP生成刺激剂）的MMQ细胞内的cAMP浓度。这种抑制作用又可被多巴胺拮抗剂氟哌啶醇和百日咳毒素（一种GTP结合偶联蛋白的灭活剂）逆转。多巴胺还可降低已暴露于钙通道激活剂 maitotoxin的MMQ细胞对45Ca2+的摄取和分数流出。因此，多巴胺似乎至少部分通过降低细胞内cAMP水平和钙摄取来减少MMQ细胞释放PRL。在其他实验中，我们发现MMQ细胞对生长抑素、雌激素、孕酮和乙酰胆碱有反应，但对促甲状腺激素释放激素（TRH）、血管紧张素II、神经降压素或蛙皮素无反应。此外，这些细胞具有功能性蛋白激酶C系统，这可通过用佛波酯处理后PRL释放增加和刺激的细胞内cAMP水平降低得到证明。我们认为，MMQ细胞系将被证明是一个有用的模型系统，用于研究多巴胺和其他影响PRL释放的因素的生化作用。
