CALCIUM IN ADRENAL CHROMAFFIN CELL FUNCTION

肾上腺中儿茶酚胺的Ca ~（2+）依赖性胞吐释放 髓质嗜铬细胞是肾上腺功能的基础 髓质，并具有重要的心血管和代谢作用。 它还 作为儿茶酚胺和其他神经递质胞吐的模型 以及神经末梢和细胞中的激素。 牛肾上腺嗜铬细胞 烟碱受体诱导的细胞内Ca ~（2+）增加 内流是胞吐作用的生理触发器。 在这份提案中，三 关于Ca 2+的代谢和影响的主题， 在控制胞吐作用或其他嗜铬细胞功能中很重要 将研究：1）Ca 2+螯合-由 促分泌素升高胞质Ca 2+，这反过来触发胞吐作用。 随后的钙螯合可能有助于终止 分泌物 在实验上，促分泌素诱导的45 Ca 2+摄取是快速的， 与世隔绝 短期钙螯合的位点将是 研究了 2)磷脂酰肌醇代谢和释放 肌醇磷酸-中试实验表明烟碱激动剂和 升高的K+是促分泌素以及毒蕈碱激动剂， 不是促分泌素，刺激肌醇磷酸的释放， 嗜铬细胞 将调查以下可能性 促分泌素诱导的细胞内Ca 2+增加可诱导 肌醇磷酸，可能通过激活钙依赖酶 脂酶C已 1，4，5-三磷酸肌醇的释放能力 还将研究来自毛地黄皂苷透化细胞的Ca 2+。 第三章 Ca 2+刺激的腺苷酸环化酶-细胞环AMP的量是 烟碱激动剂刺激以Ca 2+依赖性方式增加。 它 增加不太可能是由直接烟碱受体引起的 腺苷酸环化酶的刺激。 Ca 2+和钙调素刺激腺苷酸 某些组织细胞膜中的环化酶。 增加的可能性 胞浆Ca 2+激活嗜铬细胞中原位腺苷酸环化酶， 追究

The Ca2+-dependent, exocytotic release of catecholamine from adrenal medullary chromaffin cells is fundamental to the function of the adrenal medulla and has important cardiovascular and metabolic effects. It also serves as a model for exocytosis of catecholamine, other neurotransmitters and hormones from nerve terminals and cells. In bovine adrenal chromaffin cells nicotinic receptor-induced increase in cytosolic Ca2+ caused by Ca2+ influx is the physiological trigger for exocytosis. In this proposal three subjects concerning the metabolism and effects of Ca2+ that are possibly important in the control of exocytosis or other chromaffin cell functions will be investigated: 1) Ca2+ sequestration - Ca2+ entry induced by secretagogue raises cytosolic Ca2+ which in turn triggers exocytosis. Subsequent sequestration of Ca2+ probably contributes to the termination of secretion. Experimentally, secretagogue-induced 45Ca2+ uptake is rapidly sequestered. The site of short-term Ca2+ sequestration will be investigated. 2) Phosphatidylinositol metabolism and the release of inositol phosphates - Pilot experiments indicate the nicotinic agonists and elevated K+ which are secretagogues as well as muscarinic agonists which are not secretagogues, stimulate the release of inositol phosphates from chromaffin cells. The possibility will be investigated that secretagogue-induced increase in cytosolic Ca2+ induces the release of inositol phosphates, perhaps by activation of the Ca2+-dependent enzyme phospholipase C. The ability of inositol 1,4,5 trisphosphate to release Ca2+ from digitonin-permeabilized cells will also be investigated. 3) Ca2+-stimulated adenylate cyclase - The amount of cellular cyclic AMP is increased in a Ca2+-dependent manner by nicotinic agonist stimulation. It is unlikely that the increase is caused by direct nicotinic receptor stimulation of adenylate cyclase. Ca2+ and calmodulin stimulate adenylate cyclase in membranes from some tissues. The possibility that increases in cytosolic Ca2+ activates adenylate cyclase in situ in chromaffin cells will be investigated.