Anesthetics inhibit membrane receptor coupling to the Gq/11 heterotrimeric G protein in airway smooth muscle.
Anesthetics inhibit membrane receptor coupling to the Gq/11 heterotrimeric G protein in airway smooth muscle.
复制标题
麻醉剂抑制气道平滑肌中膜受体与 Gq/11 异源三聚体 G 蛋白的偶联。
DOI：
10.1097/00000542-200508000-00013
复制
发表时间：
2005
期刊：
影响因子：
8.8
通讯作者：
Jones,KeithA
中科院分区：
文献类型：
--
作者：
Nakayama,Tetsuzo;Hayashi,Masao;Warner,DavidO;Jones,KeithA
背景一些麻醉药部分地通过抑制乙酰胆碱引起的钙敏感性的增加来松弛气道平滑肌，这种作用与抑制Gq/11(Galphaq/11)异源三聚体G蛋白的α亚基的鸟苷核苷酸交换有关。本研究验证了这一假说，即这些麻醉效应不是M受体所特有的，而是七螺旋受体的普遍特性，它增加了气道平滑肌对钙的敏感性。方法在金黄色葡萄球菌α毒素通透性的猪气道平滑肌条上，观察麻醉对激动剂诱导的钙敏感性增加的影响。测定了麻醉对基础(无激动剂刺激)和激动剂促进的Galphaq/11鸟苷核苷酸交换的影响。结果乙酰胆碱、内皮素-1和组胺均可引起钙离子敏感性的浓度依赖性增加。氟烷(0.67+/-0.07 mM)和正己醇(10 MM)可显著抑制这两种激动剂引起的钙敏感性增加。每种激动剂还引起时间和浓度依赖的Galphaq/11核苷酸交换增加。两种麻醉剂均不影响Galphaq/11基础核苷酸交换，而氟烷和正己醇显著抑制各自激动剂促进的Galphaq/11核苷酸交换增加。结论某些麻醉药抑制激动剂促进的Galphaq/11核苷酸交换可能是七螺旋受体的共性，参与Galphaq/11介导的细胞过程，包括毒鼠碱、内皮素-1和组胺受体对钙敏感性的激活。
BackgroundSome anesthetics relax airway smooth muscle in part by inhibiting acetylcholine-induced increases in Ca2+ sensitivity, an effect associated with inhibition of guanosine nucleotide exchange at the alpha subunit of the Gq/11 (Galphaq/11) heterotrimeric G protein. This study tested the hypothesis that these anesthetic effects are not unique to the muscarinic receptor but are a general property of the heptahelical receptors that increase Ca2+ sensitivity in airway smooth muscle.MethodsAnesthetic effects on agonist-induced increases in Ca2+ sensitivity were measured in porcine airway smooth muscle strips permeabilized with S. aureus alpha-toxin. Anesthetic effects on basal (without agonist stimulation) and agonist-promoted Galphaq/11 guanosine nucleotide exchange were determined in crude membranes prepared from porcine airway smooth muscle. The nonhydrolyzable, radioactive form of guanosine 5'-triphosphate was used as the reporter for nucleotide exchange at Galphaq/11.ResultsAcetylcholine, endothelin-1, and histamine caused a concentration-dependent increase in Ca2+ sensitivity. Halothane (0.67+/-0.07 mM) and hexanol (10 mM) significantly inhibited the increase in Ca2+ sensitivity induced by each agonist. Each agonist also caused a time-and concentration-dependent increase in Galphaq/11 nucleotide exchange. Neither anesthetic had an effect on basal Galphaq/11 nucleotide exchange, whereas halothane and hexanol significantly inhibited the increase in Galphaq/11 nucleotide exchange promoted by each agonist.ConclusionThese data suggest that inhibition of agonist-promoted guanosine nucleotide exchange at Galphaq/11 by some anesthetics may be a general property of heptahelical receptors involved cellular processes mediated by Galphaq/11, including muscarinic, endothelin-1, and histamine receptor activation of Ca2+ sensitivity.