Isoflurane increases the apparent agonist affinity of the nicotinic acetylcholine receptor.
Isoflurane increases the apparent agonist affinity of the nicotinic acetylcholine receptor.
复制标题
异氟烷增加烟碱乙酰胆碱受体的表观激动剂亲和力。
DOI：
10.1097/00000542-199901000-00019
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
背景挥发性全身麻醉药增加激动剂介导的通过γ-氨基丁酸（A）、甘氨酸和5-羟色胺3（5-HT 3）受体的离子通量。这一作用反映了这些受体的表观激动剂亲和力的麻醉诱导增加。相反，挥发性麻醉剂阻断离子通过烟碱乙酰胆碱受体（nAcChoR）。作者测试的假设，除了阻止离子通量通过nAcChoR，异氟烷也增加了表观亲和力的nAcChoR为agonist.MethodsNicotinic乙酰胆碱受体获得的电鳐的electroplax器官。使用新的停流荧光测定法测定nAcChoR的表观激动剂亲和力。该测定衍生的nAcChoR的表观激动剂亲和力的激动剂转换nAcChoRs从静息状态的脱敏states.ResultsIsoflurane显着增加的nAcChoR在临床相关浓度的乙酰胆碱的表观亲和力（降低表观解离常数）的表观速率。表观解离常数呈指数下降，从44+/-4 microM到1.0+/-0.1 microM在1.5 mM的异氟烷，最高浓度studied.ConclusionsIsoflurane的存在下，异氟烷浓度的控制值增加的nAcChoR的表观激动剂的亲和力，但是，这种影响是很难解决的离子通量的研究，因为异氟烷也会导致通道阻滞。即使在相对较高的异氟烷浓度下，异氟烷对表观激动剂亲和力的影响也不饱和，这与单一麻醉作用部位相矛盾。然而，这与异氟烷与表现出一系列麻醉亲和力的几个受体位点、膜脂质内的位点或两者的相互作用一致。
BackgroundVolatile general anesthetics increase agonist-mediated ion flux through the gamma-aminobutyric acid (A), glycine, and 5-hydroxytryptamine3 (5-HT3) receptors. This action reflects an anesthetic-induced increase in the apparent agonist affinity of these receptors. In contrast, volatile anesthetics block ion flux through the nicotinic acetylcholine receptor (nAcChoR). The authors tested the hypothesis that in addition to blocking ion flux through the nAcChoR, isoflurane also increases the apparent affinity of the nAcChoR for agonist.MethodsNicotinic acetylcholine receptors were obtained from the electroplax organ of Torpedo nobiliana. The apparent agonist affinity of the nAcChoR was determined using a new stopped-flow fluorescence assay. This assay derives the apparent agonist affinity of the nAcChoR from the apparent rates with which agonists convert nAcChoRs from the resting state to the desensitized state.ResultsIsoflurane significantly increased the apparent affinity (decreased the apparent dissociation constant) of acetylcholine for the nAcChoR at clinically relevant concentrations. The apparent dissociation constant decreased exponentially with the isoflurane concentration from a control value of 44+/-4 microM to 1.0+/-0.1 microM in the presence of 1.5 mM isoflurane, the highest concentration studied.ConclusionsIsoflurane increases the apparent agonist affinity of the nAcChoR; however, this effect is poorly resolved in ion flux studies because isoflurane also causes channel blockade. The lack of saturation of isoflurane's effect on the apparent agonist affinity even at relatively high isoflurane concentrations argues against a single site of anesthetic action. However, it is consistent with isoflurane interactions with several receptor sites that exhibit a range of anesthetic affinities, sites within the membrane lipid, or both.