体外培养大鼠胰腺中淀粉酶分泌过程中钙与环核苷酸的相互作用

Calcium and cyclic nucleotide interaction in secretion of amylase from rat pancreas in vitro.

作者信息

Singh M

出版信息

J Physiol. 1979 Nov;296:159-76. doi: 10.1113/jphysiol.1979.sp012997.

DOI:10.1113/jphysiol.1979.sp012997

PMID:93637

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1279070/

Abstract

Interaction of Ca2+ and cyclic nucleotides in stimulus-secretion coupling in rat pancreas in vitro was studied utilizing the divalent cation inophore A23187. phosphodiesterase inhibitors, cyclic nucleotides and cholera toxin. 2. Amylase secretion was increased by the ionophore in the presence of extracellular Ca2+ in a dose-dependent fashion. Activation of CCK-PZ receptors simultaneously with induction of amylase secretion by A23187 did not alter amylase secretion whereas theophylline or caffeine had effects additive to A23187. Dibutyryl cyclic AMP potentiated the effect of ionophore whereas dibutyryl cyclic GMP had no effect on basal or ionophore-induced amylase secretion. Cholera toxin by itself did not effect amylase secretion whereas it potentiated the effect of ionophore. 3. A23187 increased bidirectional fluxes of 45Ca and increased efflux of 45Ca in a fashion similar to CCK-PZ. Theophylline did not alter basal efflux of 45Ca. Dibutyryl cyclic AMP increased the basal efflux of 45Ca whereas, cholera toxin, dibutyryl cyclic GMP and sodium butyrate had no effect. 4. Theophylline increased basal cyclic AMP levels with a peak effect observed at 5 min. Combination of theophylline and ionophore did not lead to an increase in levels of cyclic AMP greater than that observed with theophylline alone. Cholera toxin increased cyclic AMP levels at 30 and 60 min of incubation. 5. Ionophore and CCK-PZ increased tissue cyclic GMP levels significantly greater than that obtained with theophylline alone. This effect was dependent on extracellular Ca2+. The effect of ionophore on tissue levels of cyclic GMP could be dissociated from its effect on 45Ca efflux and amylase secretion. 6. It is concluded from these studies that Ca2+ plays a predominant role in regulating amylase secretion with interactions occurring between Ca2+ and cyclic AMP and Ca2+ and cyclic GMP. It appears that by themselves cyclic AMP and cyclic GMP do not play a significant role in regulating enzyme secretion.

摘要

利用二价阳离子载体A23187、磷酸二酯酶抑制剂、环核苷酸和霍乱毒素，研究了体外大鼠胰腺刺激-分泌偶联过程中Ca2+与环核苷酸的相互作用。2. 在细胞外Ca2+存在的情况下，离子载体以剂量依赖的方式增加淀粉酶分泌。在A23187诱导淀粉酶分泌的同时激活CCK-PZ受体不会改变淀粉酶分泌，而茶碱或咖啡因对A23187有相加作用。二丁酰环腺苷酸增强离子载体的作用，而二丁酰环鸟苷酸对基础或离子载体诱导的淀粉酶分泌无影响。霍乱毒素本身不影响淀粉酶分泌，但能增强离子载体的作用。3. A23187增加45Ca的双向通量，并以类似于CCK-PZ的方式增加45Ca的外流。茶碱不改变45Ca的基础外流。二丁酰环腺苷酸增加45Ca的基础外流，而霍乱毒素、二丁酰环鸟苷酸和丁酸钠无影响。4. 茶碱增加基础环腺苷酸水平，在5分钟时观察到峰值效应。茶碱和离子载体联合使用不会导致环腺苷酸水平的增加超过单独使用茶碱时观察到的水平。霍乱毒素在孵育30和60分钟时增加环腺苷酸水平。5. 离子载体和CCK-PZ显著增加组织环鸟苷酸水平，高于单独使用茶碱时获得的水平。这种效应依赖于细胞外Ca2+。离子载体对组织环鸟苷酸水平的影响与其对45Ca外流和淀粉酶分泌的影响可分离。6. 从这些研究得出结论，Ca2+在调节淀粉酶分泌中起主要作用，Ca2+与环腺苷酸和Ca2+与环鸟苷酸之间存在相互作用。似乎环腺苷酸和环鸟苷酸本身在调节酶分泌中不起重要作用。