The unusual nature of epibatidine responses at the α4β2 nicotinic acetylcholine receptor
The unusual nature of epibatidine responses at the α4β2 nicotinic acetylcholine receptor
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DOI：
10.1016/s0028-3908(00)00158-1
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发表时间：
2000-01-01
影响因子：
4.7
通讯作者：
Bertrand, D
中科院分区：
文献类型：
--
作者：
Buisson, B;Vallejo, YF;Bertrand, D
赤道蛙毒素，epibatidine，作为一种有效的非吗啡类镇痛药，神经元烟碱乙酰胆碱受体的选择性的鉴定，引起了显着的更新，我们的理解疼痛及其机制。在这项工作中，我们研究了地棘蛙素在主要脑大鼠α 4 β 2烟碱乙酰胆碱受体的细胞系中表达的影响。快速药物的应用程序获得了一个修改后的液体细丝系统被用于分析的电流引起的乙酰胆碱，尼古丁和地棘蛙素。地棘蛙素反应的特点是缓慢的开始和抵消，幅度较小的乙酰胆碱或尼古丁引起的。α 4 β 2受体对地棘蛙素的敏感性比对乙酰胆碱的敏感性高约1000倍，对这种化合物也表现出更明显的脱敏作用。最后，过夜暴露于1 nM地棘蛙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α 4 β 2受体上，地棘蛙素作为部分激动剂，在不激活受体的浓度下引起激动剂诱发电流的显著抑制。(C)2000爱思唯尔科技有限公司版权所有。
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 alpha4 beta2 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 alpha4 beta2 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 alpha4 beta2 receptor, epibatidine acts as a partial agonist causing a pronounced inhibition of agonist evoked currents at concentrations that do not activate the receptors. (C) 2000 Elsevier Science Ltd. All rights reserved.