The alkyl chain dependence of the effect of normal alcohols on agonist-induced nicotinic acetylcholine receptor desensitization kinetics.
The alkyl chain dependence of the effect of normal alcohols on agonist-induced nicotinic acetylcholine receptor desensitization kinetics.
复制标题
正常醇对激动剂诱导的烟碱乙酰胆碱受体脱敏动力学影响的烷基链依赖性。
DOI：
10.1097/00000542-199907000-00031
复制
发表时间：
1999
期刊：
影响因子：
8.8
通讯作者：
Zachariah,VT
中科院分区：
文献类型：
--
作者：
Raines,DE;Zachariah,VT
研究背景nAcChoR是配体门控离子通道超家族的典型成员，这些离子通道都是麻醉剂的相关靶点，并且在长时间暴露于激动剂时会发生脱敏。本研究旨在探讨代表性的正常醇对乙酰胆碱诱导的nAcChoR脱敏的表观速率的影响。用停流荧光法测定了乙酰胆碱在正常醇存在和不存在下的表观脱敏率。（研究时间最长的）增加了低浓度乙酰胆碱诱导的表观脱敏率，使脱敏的激动剂浓度-反应曲线向左偏移乙醇丁醇，并且，在较小程度上，己醇增加由高饱和浓度激动剂诱导的最大脱敏速率。除了己醇，庚醇和辛醇没有影响，这个最大的表观脱敏率，即使在浓度接近那些直接诱导脱敏在没有agonist.ConclusionNormal醇范围从乙醇到辛醇增加nAcChoR的表观亲和力的激动剂的效力是成比例的，其疏水性。然而，正常酒精对脱敏速率常数的影响显示出超出己醇的截止值。这表明正常酒精对nAcChoR脱敏的表观激动剂亲和力和速率常数的影响可能受到具有不同空间限制的不同位点的调节;研究中心负责增加最大脱敏速率的那些被预测为小于增加表观激动剂亲和力的那些。
BackgroundThe nAcChoR is the prototypical member of a superfamily of ligand-gated ion channels that are all relevant targets of anesthetics and undergo desensitization upon prolonged exposure to agonist. This study was designed to investigate the effects of representative normal alcohols on the apparent rate of acetylcholine-induced nAcChoR desensitization.MethodsNicotinic acetylcholine receptors were obtained from the electroplax organ of Torpedo nobiliana. The apparent rate of acetylcholine-induced desensitization in the presence and absence of normal alcohols was measured using stopped-flow fluorescence.ResultsNormal alcohols as long as octanol (the longest studied) increased the apparent rate of desensitization induced by low concentrations of acetylcholine, shifting the agonist concentration-response curve for desensitization to the left Ethanol butanol, and, to a lesser extent, hexanol increased the maximal rate of desensitization induced by high, saturating concentrations of agonist. Beyond hexanol, heptanol and octanol had no effect on this maximal apparent rate of desensitization, even at concentrations that approach those that directly induce desensitization in the absence of agonist.ConclusionNormal alcohols ranging from ethanol to octanol increase the apparent affinity of nAcChoR for agonist with potencies that are proportional to their hydrophobicities. However, normal alcohol effects on the rate constant for desensitization show a cutoff beyond hexanoL This suggests that the effects of normal alcohols on the apparent agonist affinity and rate constant for desensitization of nAcChoR may be modulated by distinct sites that have different steric constraints; the site (s) responsible for increasing the maximal rate of desensitization are predicted to be smaller than those that increase the apparent agonist affinity.
登录
查看更多内容
乙酰胆碱受体：来自加州鱼雷 electroplax 的膜囊泡中乙酰胆碱的电压依赖性调节（抑制）位点的表征。
影响因子：
2.9
作者：
K. Takeyasu;S. Shiono;J. Udgaonkar;N. Fujita;G. P. Hess
通讯作者：
G. P. Hess
影响因子：
3.6
作者：
S. Forman;K. Miller;G. Yellen
通讯作者：
S. Forman;K. Miller;G. Yellen
酒精和挥发性麻醉剂对烟碱乙酰胆碱受体通道激活的影响。
影响因子：
3.6
作者：
Y. Liu;J. Dilger;A. Vidal
通讯作者：
A. Vidal
乙醇稳定鱼雷烟碱乙酰胆碱受体的开放通道状态。
影响因子：
3.6
作者：
Wu,G;Tonner,PH;Miller,KW
通讯作者：
Miller,KW
不带电荷的烟碱非竞争性拮抗剂的光掺入揭示了激动剂诱导的乙酰胆碱受体 M2 区域结构的变化。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
White,BH;Cohen,JB
通讯作者：
Cohen,JB