Buisson B, Vallejo Y F, Green W N, Bertrand D
Department of Physiology, Medical Faculty, 1, rue Michel Servet, CH 1211, Geneva, Switzerland.
Neuropharmacology. 2000 Oct;39(13):2561-9. doi: 10.1016/s0028-3908(00)00158-1.
The identification of an equatorial frog toxin, epibatidine, as a potent non-morphinic analgesic, selective for neuronal nicotinic acetylcholine receptors, provoked a marked renewal in our understanding of pain and its mechanisms. In this work we have examined the effects of epibatidine at the major brain rat alpha4beta2 nicotinic acetylcholine receptor expressed in a cell line. Fast drug applications obtained with a modified liquid filament system were used for the analyses of the currents evoked by acetylcholine, nicotine and epibatidine. Characterized by a slow onset and offset, epibatidine responses were of smaller amplitude to those evoked by acetylcholine or nicotine. About a thousand times more sensitive to epibatidine than acetylcholine, the alpha4beta2 receptor also displayed a more pronounced apparent desensitization to this compound. Finally, overnight exposure to 1 nM epibatidine failed to produce the functional upregulation observed with nicotine. These data indicate that, at the rat alpha4beta2 receptor, epibatidine acts as a partial agonist causing a pronounced inhibition of agonist evoked currents at concentrations that do not activate the receptors.
一种赤道蛙毒素——埃博霉素（epibatidine）被鉴定为一种强效的非吗啡类镇痛药，对神经元烟碱型乙酰胆碱受体具有选择性，这使我们对疼痛及其机制的理解有了显著的更新。在这项研究中，我们检测了埃博霉素对在细胞系中表达的大鼠主要脑α4β2烟碱型乙酰胆碱受体的影响。使用改良的液体细丝系统进行快速药物应用，以分析乙酰胆碱、尼古丁和埃博霉素诱发的电流。埃博霉素的反应具有缓慢的起始和终止特征，其幅度小于乙酰胆碱或尼古丁诱发的反应。α4β2受体对埃博霉素的敏感性比对乙酰胆碱高约一千倍，对该化合物也表现出更明显的明显脱敏现象。最后，过夜暴露于1 nM埃博霉素未能产生尼古丁所观察到的功能上调。这些数据表明，在大鼠α4β2受体上，埃博霉素作为一种部分激动剂，在不激活受体的浓度下对激动剂诱发的电流产生明显抑制作用。
