The role of electrostatic interactions in governing anesthetic action on the torpedo nicotinic acetylcholine receptor.
The role of electrostatic interactions in governing anesthetic action on the torpedo nicotinic acetylcholine receptor.
复制标题
静电相互作用在控制鱼雷烟碱乙酰胆碱受体麻醉作用中的作用。
DOI：
10.1097/00000539-200208000-00021
复制
发表时间：
2002
影响因子：
5.7
通讯作者：
Claycomb,RobertJ
中科院分区：
文献类型：
--
作者：
Raines,DouglasE;Claycomb,RobertJ
Isoflurane and normal alkanols reduce the apparent agonist dissociation constant (K d) of the nicotinic acetylcholine receptor (nAChR) at clinically relevant concentrations, whereas cyclopropane and butane do not. This suggests that electrostatic (hydrogen bonding and/or dipolar) interactions modulate anesthetic potency in this model receptor system. To further define the nature of these interactions, we quantified the potencies with which a heterologous group of general anesthetics reduces the nAChR’s apparent K d for acetylcholine. We assessed the importance that an anesthetic’s molecular volume, ability to donate a hydrogen bond (hydrogen bond acidity), ability to accept a hydrogen bond (hydrogen bond basicity), and dipole moment play in determining aqueous potency. We found that aqueous anesthetic potency increases with molecular volume and decreases with hydrogen bond basicity but is unaffected by dipole moment and hydrogen bond acidity. These results suggest that anesthetics reduce the apparent agonist K d of the nAChR by binding to a site that has a dipolarity and ability to accept hydrogen bonds that are similar to those of water, but a hydrogen bond-donating capacity that is less.
