Wong E T, Holstad S G, Mennerick S J, Hong S E, Zorumski C F, Isenberg K E
Department of Neurology, Washington University School of Medicine, St. Louis, MO.
Brain Res Mol Brain Res. 1995 Jan;28(1):101-9. doi: 10.1016/0169-328x(94)00189-l.
Neuronal nicotinic acetylcholine receptor subunits alpha 3 (PCA48E) and beta 4S (ZPC13) were expressed in human embryonic kidney (HEK)-293 cells by calcium phosphate transfection. In the presence of atropine, acetylcholine (ACh) induced fast activating currents which exhibited desensitization and inward rectification. The EC50 for ACh was 202 +/- 32 microM with a Hill coefficient of 1.9 +/- 0.4. The rank order of nicotinic agonist potency was 1,1-dimethyl-4-phenylpiperozinium (DMPP) > cytisine = nicotine approximately equal to ACh. The maximal response elicited by DMPP was substantially less than that elicited by other agonists, suggesting that DMPP is a partial agonist. ACh (500 microM) responses were very effectively blocked by equimolar concentrations (100 microM) of the ganglionic antagonists d-tubocurarine, mecamylamine and hexamethonium. Equal concentrations of the potent muscle receptor antagonist decamethonium and the competitive antagonist dihydro-beta-erythroidine were much less effective. alpha bungaro-toxin (1 microM) had little effect on ACh-induced responses. This physiological and pharmacological profile is consistent with a ganglionic nicotinic response.
通过磷酸钙转染，将神经元烟碱型乙酰胆碱受体亚基α3（PCA48E）和β4S（ZPC13）在人胚肾（HEK）-293细胞中表达。在阿托品存在的情况下，乙酰胆碱（ACh）诱导快速激活电流，该电流表现出脱敏和内向整流。ACh的EC50为202±32μM，希尔系数为1.9±0.4。烟碱激动剂效力的顺序为1,1-二甲基-4-苯基哌嗪鎓（DMPP）>金雀花碱 = 尼古丁≈ACh。DMPP引发的最大反应明显小于其他激动剂引发的反应，表明DMPP是一种部分激动剂。ACh（500μM）反应被等摩尔浓度（100μM）的神经节拮抗剂d-筒箭毒碱、美加明和六甲铵非常有效地阻断。等浓度的强效肌肉受体拮抗剂十烃季铵和竞争性拮抗剂二氢β-刺桐啶的效果要差得多。α-银环蛇毒素（1μM）对ACh诱导的反应影响很小。这种生理和药理学特征与神经节烟碱反应一致。
