Sung C K, Williams J A
Department of Physiology, University of California, San Francisco.
Miner Electrolyte Metab. 1988;14(1):71-7.
Early studies provided indirect evidence of an intracellular messenger role for Ca2+ in pancreatic stimulus-secretion coupling. Recent development of Ca2+-selective fluorescent indicators has now allowed direct measurement of the cytoplasmic free Ca2+ concentration [( Ca2+]i). Using quin 2, resting [Ca2+]i values of 90-160 nM have been determined in the pancreatic acinar cells of mouse, guinea pig and rat. Upon stimulation with carbamylcholine (CCh) or cholecystokinin (CCK), [Ca2+]i increased within seconds by 4- to 8-fold. Studies of amylase release and the [Ca2+]i increase revealed a stoichiometric relationship at submaximal CCh concentrations although amylase release at supramaximal secretagogue concentrations decreased while peak [Ca2+] remained elevated. The failure of Ca2+ ionophores to stimulate full amylase release in proportion to the rise in Ca2+, along with the short duration of the increase in [Ca2+]i induced by secretagogues, suggest that Ca2+ is not the sole determinant of amylase release. Studies of amylase release and protein phosphorylation suggest that 1,2-diacylglycerol produced by the secretagogue-induced breakdown of phosphatidylinositol-4,5-bisphosphate (PIP2) also mediates secretion and may act synergistically with Ca2+ to alter the phosphorylation of structural and regulatory acinar cell proteins.
早期研究提供了钙离子在胰腺刺激-分泌偶联中作为细胞内信使作用的间接证据。钙离子选择性荧光指示剂的最新发展现已允许直接测量细胞质游离钙离子浓度[（Ca2+）i]。使用喹啉2，已测定小鼠、豚鼠和大鼠胰腺腺泡细胞中静息[Ca2+]i值为90 - 160 nM。用氨甲酰胆碱（CCh）或胆囊收缩素（CCK）刺激后，[Ca2+]i在数秒内增加4至8倍。对淀粉酶释放和[Ca2+]i增加的研究表明，在亚最大CCh浓度下存在化学计量关系，尽管在超最大促分泌素浓度下淀粉酶释放减少，而[Ca2+]峰值仍保持升高。钙离子载体不能按钙离子升高比例刺激完全淀粉酶释放，以及促分泌素诱导的[Ca2+]i增加持续时间短，这表明钙离子不是淀粉酶释放的唯一决定因素。对淀粉酶释放和蛋白质磷酸化的研究表明，促分泌素诱导的磷脂酰肌醇-4,5-二磷酸（PIP2）分解产生的1,2-二酰基甘油也介导分泌，并且可能与钙离子协同作用以改变腺泡细胞结构和调节蛋白的磷酸化。
