Halothane does not inhibit the functional coupling between the beta2-adrenergic receptor and the Galphas heterotrimeric G protein.
Halothane does not inhibit the functional coupling between the beta2-adrenergic receptor and the Galphas heterotrimeric G protein.
复制标题
氟烷不会抑制 β2-肾上腺素受体和 Galphas 异三聚体 G 蛋白之间的功能偶联。
DOI：
10.1097/00000542-200604000-00020
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发表时间：
2006
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：
Hayashi,Masao;Penheiter,SumedhaG;Nakayama,Tetsuzo;Penheiter,AlanR;Warner,DavidO;Jones,KeithA
本研究探讨氟烷是否影响β 2肾上腺素能受体与其同源刺激性异源三聚体鸟苷-5 '-三磷酸（GTP）结合蛋白（Galphas）α亚基之间的功能偶联。作者假设，氟烷不影响异丙肾上腺素促进鸟苷酸交换在Galphas，因此不会影响异丙肾上腺素诱导的松弛气道smoothmuscles.MethodsHalothane对异丙肾上腺素诱导的钙敏感性抑制的影响进行了测定透化猪气道平滑肌。在从COS-7细胞制备的粗膜中测量Galphas核苷酸交换，COS-7细胞被转染以瞬时共表达人β 1或β 2受体，每个受体与人短Galphas。一个放射性的，nonhydrolyzable类似物的GTP，[S] GTP gammaS，被用作报告的核苷酸交换在Galphas.ResultsHalothane（0.75毫米，约2.8最低肺泡浓度[MAC]在猪）不影响异丙肾上腺素诱导的钙敏感性抑制。异丙肾上腺素引起Galphas核苷酸交换的时间和浓度依赖性增加。氟烷，即使在浓度为1.5毫米（约5.6 MAC），有基础的Galphas核苷酸交换在异丙肾上腺素的情况下，没有影响，而氟烷抑制异丙肾上腺素促进Galphas核苷酸交换的β 1-Galphas和β 2-Galphas表达膜。然而，效果是显着更大的β 1-Galphas耦合与β 2-Galphas耦合相比，没有影响β 2-Galphas耦合在2.8 MAC halothane.ConclusionHalothane不抑制β 2受体和Galphas之间的生物化学耦合，因此不影响异丙肾上腺素诱导的钙敏感性的抑制。因此，氟烷不应影响β 2受体激动剂的疗效，如体内哮喘动物模型研究所示。
BackgroundThis study investigated whether halothane affects the functional coupling between the beta2 adrenergic receptor and the alpha subunit of its cognate stimulatory heterotrimeric guanosine-5'-triphosphate (GTP)-binding protein (Galphas). The authors hypothesized that halothane does not affect isoproterenol-promoted guanosine nucleotide exchange at Galphas and hence would not affect isoproterenol-induced relaxation of airway smooth muscle.MethodsHalothane effects on isoproterenol-induced inhibition of calcium sensitivity were measured in permeabilized porcine airway smooth muscle. Galphas nucleotide exchange was measured in crude membranes prepared from COS-7 cells transfected to transiently coexpress the human beta1 or beta2 receptor each with human short Galphas. A radioactive, nonhydrolyzable analog of GTP,[S] GTPgammaS, was used as the reporter for nucleotide exchange at Galphas.ResultsHalothane (0.75 mm, approximately 2.8 minimum alveolar concentration [MAC] in pigs) did not affect isoproterenol-induced inhibition of calcium sensitivity. Isoproterenol caused a time-and concentration-dependent increase in Galphas nucleotide exchange. Halothane, even at concentrations of 1.5 mm (approximately 5.6 MAC), had no effect on basal Galphas nucleotide exchange in the absence of isoproterenol, whereas halothane inhibited isoproterenol-promoted Galphas nucleotide exchange in both the beta1-Galphas and beta2-Galphas expressing membranes. However, the effect was significantly greater on beta1-Galphas coupling compared with beta2-Galphas coupling, with no effect on beta2-Galphas coupling at 2.8 MAC halothane.ConclusionHalothane does not inhibit the biochemical coupling between the beta2 receptor and Galphas and hence does not affect the inhibition of calcium sensitivity induced by isoproterenol. Therefore, halothane should not affect the efficacy of beta2 agonists, as suggested by studies of in vivo animal models of asthma.