Mathias P C, Carpinelli A R, Billaudel B, Garcia-Morales P, Valverde I, Malaisse W J
Biochem Pharmacol. 1985 Oct 1;34(19):3451-7. doi: 10.1016/0006-2952(85)90717-8.
Cholinergic agents are known to stimulate the hydrolysis of polyphosphoinositides in pancreatic islets. The effect of carbamylcholine upon ion fluxes in the islet cells was investigated. Carbamylcholine provoked a rapid but poorly sustained increase in 45Ca and 86Rb outflow from perifused islets. Such a cationic response was observed at different glucose concentrations (zero to 16.7 mM), at three concentrations of carbamylcholine (10 microM, 100 microM and 1.0 mM), and in the absence or presence of extracellular Ca2+. It coincided with a biphasic stimulation of insulin release, both the cationic and secretory responses being abolished in the presence of atropine (10 microM). At variance with nutrient secretagogues, carbamylcholine failed to affect the net production of cyclic AMP and caused a transient decrease in 32P outflow from islets prelabelled with [32P]phosphate. It is proposed that cholinergic agents mobilize Ca2+ from intracellular sites, possibly through generation of inositol, 1,4,5-triphosphate from phosphatidylinositol 4,5-bisphosphate. The intracellular redistribution of Ca2+ does not appear sufficient, however, to account fully for the secretory response, which may also involve activation of protein kinase C by diacylglycerol.
已知胆碱能药物可刺激胰岛中多磷酸肌醇的水解。研究了氨甲酰胆碱对胰岛细胞离子通量的影响。氨甲酰胆碱可使灌流胰岛中45Ca和86Rb的流出迅速增加，但持续时间较短。在不同葡萄糖浓度（0至16.7 mM）、三种氨甲酰胆碱浓度（10 microM、100 microM和1.0 mM）以及有无细胞外Ca2+的情况下均观察到这种阳离子反应。它与胰岛素释放的双相刺激同时发生，在存在阿托品（10 microM）时，阳离子反应和分泌反应均被消除。与营养性促分泌剂不同，氨甲酰胆碱未能影响环磷酸腺苷的净生成，并导致预先用[32P]磷酸盐标记的胰岛中32P流出短暂减少。有人提出，胆碱能药物可能通过从磷脂酰肌醇4,5-二磷酸生成肌醇1,4,5-三磷酸，从细胞内位点动员Ca2+。然而，Ca2+的细胞内重新分布似乎不足以完全解释分泌反应，分泌反应可能还涉及二酰基甘油对蛋白激酶C的激活。
