【摘要】 目的:研究糖皮质激素皮质酮对PC12细胞烟碱受体的非基因组作用.方法:采用全细胞膜片箝技术记录神经生长因子分化的PC12细胞上的乙酰胆碱（ACh）诱发电流(I_ACh).结果:PC12细胞上I_ACh是由烟碱受体引起的.同时给予ACh（3Oμmol/L）和皮质酮（0.1-10μmol/L）加速I_ACh的衰减且轻微抑制I_ACh峰值.用相同浓度的皮质酮预处理细胞可加强对I_ACh峰值的抑制率而不影响受体失敏速率.牛血清白蛋白耦联的皮质酮（0.1-10μmol/L）对I_ACh有类似于皮质酮的快速抑制作用.此快速抑制作用呈可逆性、浓度依赖性和非电压依赖性.结论:皮质酮可快速抑制PC12细胞I_ACh,已是由非基因组机制介导的.皮质酮结合于膜外的特异结合位点,很可能直接作用于神经元烟碱受体,以一种非竞争方式抑制I_ACh,从而调控交感神经元的儿茶酚胺释放.更多还原

【Abstract】 To investigate the nongenomic effect of the glucocorticoid corticosterone on nicotinic acetylcholine receptor (nAChR) in PC12 cells. METHODS; The acetylcholine (ACh)-induced current was measured on nerve growth factor differentiated PC12 cells using whole-cell patch-clamp techniques. RESULTS: The ACh-induced current (IAch) proved to be generated through neuronal nAChR. When ACh (30 μmol/L) was applied simultaneously with corticosterone (0.1 - 10μmol/L) , the decay of IAch was faster with slight inhibition on the peak current amplitude. Pretreating PC12 cells with corticosterone augmented the inhibition on the peak IAchand did not alter receptor desensitization. Bovine serum albumin-conjugated corticosterone (0.1 - 10 /μmol/L) had the inhibition similar to corticosterone. The rapid effect induced by corticosterone was reversible, concentration-dependent, and voltage-independent. CONCLUSION: Corticosterone has rapid inhibitory effect on IAch which is mediated by a nongenomic mechanism. It indicates that corticosterone binds to the specific site on the outer cell membrane, probably on the neuronal nicotinic receptor-coupled channel, and inhibits the IAch in a noncompetitive manner, thus controlling the immediate catecholamine release from the sympathetic cells.更多还原