CHARACTERIZATION OF THE MMQ CELL, A PROLACTIN-SECRETING CLONAL CELL-LINE THAT IS RESPONSIVE TO DOPAMINE
CHARACTERIZATION OF THE MMQ CELL, A PROLACTIN-SECRETING CLONAL CELL-LINE THAT IS RESPONSIVE TO DOPAMINE
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DOI：
10.1210/endo-123-5-2341
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发表时间：
1988-11-01
期刊：
影响因子：
4.8
通讯作者：
MACLEOD, RM
中科院分区：
文献类型：
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作者：
JUDD, AM;LOGIN, IS;MACLEOD, RM
虽然多巴胺抑制PRL从正常的垂体前叶催乳素释放，一个决定性的演示参与这种反应的机制已被其他细胞类型的存在下，在垂体前叶受阻。为了解决这个问题，我们已经分离出一个克隆细胞系，命名为MMQ，从7315 a大鼠垂体瘤。MMQ细胞是我们使用的示例性模型，因为它仅分泌PRL。我们的研究表明，多巴胺抑制促分泌素诱导的PRL从这些细胞释放。此外，多巴胺降低了MMQ细胞中的细胞内cAMP浓度，MMQ细胞已暴露于毛喉素、霍乱毒素或血管活性肠多肽，每一种都是cAMP生成的刺激物。这种抑制作用反过来又被多巴胺拮抗剂氟哌啶醇和百日咳毒素逆转，百日咳毒素是GTP结合偶联蛋白的灭活剂。多巴胺还降低了MMQ细胞对45 Ca 2+的摄取和流出分数，MMQ细胞已暴露于钙通道激活剂美托毒素。因此，多巴胺似乎至少部分通过降低细胞内cAMP水平和钙摄取来降低MMQ细胞的PRL释放。在另外的实验中，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TRH、血管紧张素II、神经降压素或铃蟾肽无反应。此外，这些细胞具有功能性蛋白激酶-C系统，如通过响应于用佛波醇二酯处理而发生的PRL释放增加和刺激的细胞内cAMP水平降低所证明的。我们认为MMQ细胞系将被证明是研究多巴胺和其他改变PRL释放的因素的生化作用的有用模型系统。
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, progestrone, 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.