Dorflinger L J, Schonbrunn A
Endocrinology. 1983 Nov;113(5):1551-8. doi: 10.1210/endo-113-5-1551.
Somatostatin (SRIF) inhibits both basal and vasoactive intestinal peptide (VIP)-stimulated hormone secretion by the GH4C1 clonal strain of rat pituitary tumor cells. We have previously shown that SRIF inhibits cAMP accumulation stimulated by VIP but does not alter basal cAMP levels in this cell line. To determine the importance of changes in cAMP accumulation in the mechanism of SRIF action, we have compared the effect of SRIF on hormone release stimulated by VIP and two other secretagogues which increase effective intracellular cAMP concentrations: forskolin and 8-Bromo-cAMP (8-Br-cAMP). VIP stimulated GH and PRL secretion to the same maximal extent (220% of control) with similar ED50 values (0.37 +/- 0.03 and 0.43 +/- 0.08 nM, mean +/- SE, respectively). SRIF (100 nM) reduced maximal VIP-stimulation of both GH and PRL release from 220 to 140% of control; however, it did not significantly change the ED50 values for VIP. The effect of SRIF on VIP-stimulated hormone release parallels its action on VIP-stimulated cAMP accumulation. Furthermore, the concentrations of SRIF required to produce half-maximal inhibition of VIP-stimulated GH and PRL release (0.8 +/- 0.2 nM and 0.7 +/- 0.1 nM, respectively) were similar to its potency to inhibit VIP-stimulated cAMP accumulation (1.2 +/- 0.1 nM). These data indicate that changes in cAMP levels mediate inhibition of VIP-stimulated hormone secretion by SRIF. Forskolin increased cAMP accumulation with an ED50 value of 2.4 +/- 0.5 microM. A maximal concentration of forskolin (100 microM) stimulated cAMP accumulation to a greater extent than 100 nM VIP (34 +/- 4-fold vs. 9 +/- 1-fold). Together, forskolin (100 microM) and VIP (100 nM) stimulated cAMP accumulation by more than 50-fold. However, PRL secretion in response to maximal concentrations of VIP or forskolin individually or together were the same (approximately 200% of control). These results support the conclusion that both compounds stimulate PRL secretion by a cAMP-mediated mechanism which can be fully activated by either one alone.(ABSTRACT TRUNCATED AT 400 WORDS)
生长抑素（SRIF）可抑制大鼠垂体肿瘤细胞系GH4C1的基础激素分泌以及血管活性肠肽（VIP）刺激的激素分泌。我们之前已经表明，SRIF可抑制VIP刺激的cAMP积累，但不会改变该细胞系中的基础cAMP水平。为了确定cAMP积累变化在SRIF作用机制中的重要性，我们比较了SRIF对VIP以及其他两种可增加细胞内有效cAMP浓度的促分泌素（福斯可林和8-溴-cAMP，8-Br-cAMP）刺激的激素释放的影响。VIP刺激生长激素（GH）和催乳素（PRL）分泌达到相同的最大程度（对照的220%），且具有相似的半数有效浓度（ED50）值（分别为0.37±0.03和0.43±0.08 nM，平均值±标准误）。SRIF（100 nM）将VIP对GH和PRL释放的最大刺激作用从对照的220%降低至140%；然而，它并未显著改变VIP的ED50值。SRIF对VIP刺激的激素释放的作用与其对VIP刺激的cAMP积累的作用相似。此外，产生对VIP刺激的GH和PRL释放半数最大抑制所需的SRIF浓度（分别为0.8±0.2 nM和0.7±0.1 nM）与其抑制VIP刺激的cAMP积累的效力（1.2±0.1 nM）相似。这些数据表明，cAMP水平的变化介导了SRIF对VIP刺激的激素分泌的抑制作用。福斯可林增加cAMP积累，其ED50值为2.4±0.5 microM。福斯可林的最大浓度（100 microM）刺激cAMP积累的程度大于100 nM VIP（分别为34±4倍和9±1倍）。福斯可林（100 microM）和VIP（100 nM）共同刺激cAMP积累超过50倍。然而，单独或共同使用最大浓度的VIP或福斯可林时，PRL分泌相同（约为对照的200%）。这些结果支持以下结论：这两种化合物均通过cAMP介导的机制刺激PRL分泌，且任一化合物单独作用时均可完全激活该机制。（摘要截选至400字）
