Heisler S, Fortin A
Can J Physiol Pharmacol. 1984 Mar;62(3):309-13. doi: 10.1139/y84-048.
The possible role of calmodulin in exocytotic secretion is supported by the presence of this calcium-binding protein in secretory cells, and by the antisecretory effects in intact secretory cells of substances which can antagonize calmodulin-stimulated enzymes in broken cell preparations. In this study, two in vitro calmodulin antagonists, W-7 and chlorpromazine, were found to produce both similar and different pharmacological effects on the secretory process in rat exocrine pancreas. Both substances blocked amylase secretion in response to carbachol or cholecystokinin octapeptide, but only chlorpromazine inhibited the ability of carbachol to stimulate 45Ca efflux from isotope-preloaded cells. Only W-7 could inhibit the secretory response to vasoactive intestinal peptide (VIP); but both W-7 and chlorpromazine were equipotent partial antagonists of VIP-stimulated cyclic AMP synthesis. Chlorpromazine increased the secretory response to melittin but W-7 did not. The divergence in biological responsiveness to W-7 and chlorpromazine makes it difficult to extrapolate the in vitro effects of these agents to similar actions in intact cell systems.
分泌细胞中存在这种钙结合蛋白，以及在完整分泌细胞中，能拮抗破碎细胞制剂中钙调蛋白刺激酶的物质具有抗分泌作用，这些均支持钙调蛋白在胞吐分泌中可能发挥的作用。在本研究中，发现两种体外钙调蛋白拮抗剂W - 7和氯丙嗪，对大鼠外分泌胰腺的分泌过程产生了相似和不同的药理作用。两种物质均能阻断由卡巴胆碱或八肽胆囊收缩素引起的淀粉酶分泌，但只有氯丙嗪能抑制卡巴胆碱刺激同位素预加载细胞中45Ca外流的能力。只有W - 7能抑制对血管活性肠肽（VIP）的分泌反应；但W - 7和氯丙嗪都是VIP刺激的环磷酸腺苷合成的等效部分拮抗剂。氯丙嗪增强了对蜂毒肽的分泌反应，但W - 7没有。对W - 7和氯丙嗪生物学反应性的差异使得难以将这些药物的体外作用外推至完整细胞系统中的类似作用。
