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Menbrane phospholipase c activation and signal transduction in relation to change of receptor-linkage mechanism

膜磷脂酶 c 激活和信号转导与受体连接机制变化的关系

基本信息

批准号：
62480123
负责人：
KATO Ryuichi
金额：
$ 3.71万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

The mechanism of functional shift from muscarinic to nicotinic cholinergic receptors involved in cytosolic Ca^<++> mobilization and inositol triphosphate (IP_3) during the primary culture of adrenal chromaffin cells was studied. At 0.5 day in culture, muscarine, a specific agonist for muscarinic receptors, caused a greater effect on intracellular Ca^<2+> mobilization and the accumulation of Ins(1,3,4)P_3 than did the nicotinic-specific agonist nicotine. On the contrary, at 5 days, nicotine produced a greater effect on the accumulation of Ins(1,3,4)P_3 and intracellular calcium mobilization than did muscarine. Furthermore, at 0.5 day, the muscarinic antagonist atropine strongly inhibited the increase in InsP_3 accumulation that was induced by the nonspecific agonist carbachol, whereas at 5 days the inhibitory effect of atropine was greatly lowered. On the other hand, the nicotinic receptor antagonists hexamethonium and - tubocurarine showed a much higher inhibitory potency at 5 days compared with 0.5 day in culture. Binding experiments with a muscarinic ligand excluded the possibility that the reduction in muscarinic effects on InsP_3 and intracellular Ca^<2+> mobilization were due to disappearance of the muscarinic receptor itself. These data show that cholinergic receptors linked to the accumulation of InsP_3 and Ca^<2+> mobilization functionally shift from muscarinic to nicotinic during primary culture of adrenal chromaffin cells.

本文研究了肾上腺嗜铬细胞原代培养过程中，M胆碱能受体向烟碱能胆碱能受体参与胞浆钙动员和三磷酸肌醇(IP_3)的作用机制。培养0.5d时，M受体特异性激动剂毒扁豆碱对细胞内Ca~(2+)动员和INS(1，3，4)P_3积累的影响大于烟碱特异性激动剂尼古丁。相反，在培养5d时，尼古丁对INS(1，3，4)P3的积聚和细胞内钙动员的影响大于毒扁豆碱。在0.5d时，M受体拮抗剂阿托品可强烈抑制非特异性激动剂卡巴胆碱诱导的InSP_3蓄积增加，而在5d时，阿托品的抑制作用明显减弱。另一方面，烟碱受体拮抗剂六甲溴铵和-管库拉林在培养5d时显示出比0.5d更高的抑制效力。与M受体的结合实验排除了M受体自身消失导致M受体对InSP_3和细胞内Ca~(2+)动员减少的可能性。这些数据表明，在肾上腺嗜铬细胞原代培养过程中，与InSP_3和Ca~(2+)动员有关的胆碱能受体的功能从M胆碱能向烟碱能转变。