Effects of staurosporine on protein kinase C and amylase secretion from pancreatic acini.
Effects of staurosporine on protein kinase C and amylase secretion from pancreatic acini.
复制标题
星形孢菌素对胰腺腺泡蛋白激酶 C 和淀粉酶分泌的影响。
DOI：
10.1152/ajpgi.1989.257.4.g548
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Hootman,SR
中科院分区：
文献类型：
--
作者：
Verme,TB;Velarde,RT;Cunningham,RM;Hootman,SR
研究了星形孢碱（一种最近分离的微生物生物碱）对豚鼠胰腺腺泡淀粉酶分泌和蛋白激酶 C 活性的影响。浓度为 1 microM 的 Staurosporine 完全抑制腺泡蛋白激酶 C 活性 (IC50 = 5.5 +/- 1.4 nM) 和由佛波酯 12-O-十四烷酰佛波醇-13-乙酸酯 (TPA) 诱导的淀粉酶分泌 (IC50 = 4.1 +/- 0.4 nM)。在此浓度下，星形孢菌素使最大有效浓度的卡巴胆碱和缩胆囊素引起的淀粉酶分泌减少约50%，但没有明显改变两种促分泌剂的效力。在星形孢菌素存在的情况下，由卡巴胆碱诱导的淀粉酶分泌在至少 60 分钟内呈线性。星形孢菌素对 Ca2+ 离子载体 A23187 引起的淀粉酶释放没有影响。然而，它确实抑制血管活性肠肽诱导的分泌，尽管相对于其对 TPA、卡巴胆碱和胆囊收缩素刺激的淀粉酶释放的影响，其效力有所降低 (IC50 = 34 +/- 17 nM)。这些结果表明星形孢菌素是胰腺腺泡中蛋白激酶C活性的有效抑制剂，并且蛋白激酶C作为腺泡细胞中胆囊收缩素和卡巴胆碱诱导的消化酶分泌的细胞内介质具有重要作用。此外，一个单独的星形孢菌素不敏感偶联途径（很可能涉及 Ca2+）似乎同样重要，并且可以在缺乏功能性蛋白激酶 C 活性的情况下维持长期分泌。
The effects of staurosporine, a recently isolated microbial alkaloid, on amylase secretion and protein kinase C activity of guinea pig pancreatic acini were investigated. Staurosporine at a concentration of 1 microM completely inhibited both acinar protein kinase C activity (IC50 = 5.5 +/- 1.4 nM) and amylase secretion induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (IC50 = 4.1 +/- 0.4 nM). At this concentration, staurosporine reduced amylase secretion elicited by maximally effective concentrations of carbachol and cholecystokinin by approximately 50% but did not appreciably alter the potencies of the two secretagogues. In the presence of staurosporine, amylase secretion induced by carbachol was linear for at least 60 min. Staurosporine had no effect on amylase release elicited by the Ca2+ ionophore A23187. It did, however, inhibit secretion induced by vasoactive intestinal peptide, although with a reduced potency relative to its effects on amylase release stimulated by TPA, carbachol, and cholecystokinin (IC50 = 34 +/- 17 nM). These results indicate that staurosporine is a potent inhibitor of protein kinase C activity in pancreatic acini and that protein kinase C has an important role as an intracellular mediator of digestive enzyme secretion induced by cholecystokinin and carbachol in the acinar cell. In addition, a separate staurosporine-insensitive coupling pathway, most likely involving Ca2+, appears to be equally important and can maintain long-term secretion in the absence of functional protein kinase C activity.