Sato M, Downs T R, Frohman L A
Department of Internal Medicine, University of Cincinnati College of Medicine, OH 45267.
Peptides. 1993 Jul-Aug;14(4):671-7. doi: 10.1016/0196-9781(93)90096-y.
Signal transduction mechanisms involved in mouse growth hormone-releasing hormone (GRH) and somatostatin (SRIH) release were investigated using an in vitro perifusion system. Hypothalamic fragments were exposed to depolarizing agents, protein kinase A and C activators, and a calcium ionophore. The depolarizing agents, KCl (60 mM) and veratridine (50 microM), induced similar patterns of GRH and SRIH release. Somatostatin release in response to both agents was twofold greater than that of GRH. Forskolin (10 microM and 100 microM), an adenylate cyclase activator, stimulated both GRH and SRIH release, though with different secretory profiles. The SRIH response was prolonged and persisted beyond removal of the drug from the system, while the GRH response was brief, ending even prior to forskolin removal. Neither GRH nor SRIH were stimulated by 1,9-dideoxy-forskolin (100 microM), a forskolin analog with cAMP-independent actions. A23187 (5 microM), a calcium ionophore, stimulated the release of SRIH to a much greater extent than that of GRH. The GRH and SRIH secretory responses to PMA (1 microM), a protein kinase C activator, were similar, though delayed. The results suggest that 1) GRH and SRIH secretion are regulated by both protein kinase A and C pathways, and 2) depolarizing agents are important for the release of both hormones.
使用体外灌流系统研究了参与小鼠生长激素释放激素（GRH）和生长抑素（SRIH）释放的信号转导机制。将下丘脑片段暴露于去极化剂、蛋白激酶A和C激活剂以及钙离子载体。去极化剂氯化钾（60 mM）和藜芦碱（50 μM）诱导了相似的GRH和SRIH释放模式。对这两种试剂的生长抑素释放反应比GRH释放反应大两倍。腺苷酸环化酶激活剂福斯高林（10 μM和100 μM）刺激了GRH和SRIH的释放，尽管分泌模式不同。SRIH反应持续时间延长，在药物从系统中去除后仍持续存在，而GRH反应短暂，甚至在福斯高林去除之前就结束了。GRH和SRIH均未受到1,9-二脱氧福斯高林（100 μM）的刺激，1,9-二脱氧福斯高林是一种具有不依赖cAMP作用的福斯高林类似物。钙离子载体A23187（5 μM）刺激SRIH释放的程度比GRH大得多。蛋白激酶C激活剂佛波酯（PMA，1 μM）对GRH和SRIH的分泌反应相似，尽管有所延迟。结果表明：1）GRH和SRIH的分泌受蛋白激酶A和C途径的调节；2）去极化剂对这两种激素的释放都很重要。
