Slimak G G, Stark H A, Egan J J, Jensen R T, Gardner J D
Digestive Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Pancreas. 1993 Mar;8(2):212-9. doi: 10.1097/00006676-199303000-00012.
In dispersed acini from rat pancreas, verapamil (a phenylalkylamine calcium channel blocker) potentiated amylase secretion stimulated by vasoactive intestinal peptide (VIP), secretin, peptide histidine isoleucine, helodermin, forskolin, and 8-bromocyclic AMP. The action of verapamil on VIP-stimulated amylase secretion was detectable at 10 microM verapamil and maximal at 100 microM verapamil. Verapamil did not alter binding of 125I-VIP, basal cAMP, the increase in cAMP caused by VIP, or the increase in cAMP-dependent protein kinase caused by VIP. The effects of verapamil on stimulated amylase secretion were fully reversible and could be reproduced by nicardipine (a 1,4-dihydropyridine calcium channel blocker) and diltiazem (a benzothiazepine calcium channel blocker), but not by cinnarizine (a piperazine calcium channel blocker). Although 300 microM verapamil increased outflux of 45Ca, 100 microM verapamil, the concentration that produced maximal potentiation of VIP-stimulated amylase secretion, did not alter 45Ca outflux. Our results indicate that the action of verapamil to potentiate amylase secretion stimulated by secretagogues that activate the cAMP pathway occurs at a step that is distal to the activation of cAMP-dependent protein kinase.
在大鼠胰腺的分散腺泡中，维拉帕米（一种苯烷基胺类钙通道阻滞剂）增强了由血管活性肠肽（VIP）、促胰液素、肽组氨酸异亮氨酸、蛙皮素、福斯可林和8-溴环磷酸腺苷刺激引起的淀粉酶分泌。维拉帕米对VIP刺激的淀粉酶分泌的作用在10微摩尔/升维拉帕米时即可检测到，在100微摩尔/升维拉帕米时达到最大。维拉帕米不改变125I-VIP的结合、基础环磷酸腺苷、VIP引起的环磷酸腺苷增加或VIP引起的环磷酸腺苷依赖性蛋白激酶增加。维拉帕米对刺激的淀粉酶分泌的作用是完全可逆的，并且可以被尼卡地平（一种1,4-二氢吡啶类钙通道阻滞剂）和地尔硫䓬（一种苯并硫氮䓬类钙通道阻滞剂）重现，但不能被桂利嗪（一种哌嗪类钙通道阻滞剂）重现。虽然300微摩尔/升维拉帕米增加了45Ca外流，但100微摩尔/升维拉帕米（产生VIP刺激的淀粉酶分泌最大增强作用的浓度）并未改变45Ca外流。我们的结果表明，维拉帕米增强由激活环磷酸腺苷途径的促分泌剂刺激引起的淀粉酶分泌的作用发生在环磷酸腺苷依赖性蛋白激酶激活的下游步骤。
