Minami Kouichiro, Uezono Yasuhito, Sakurai Takeshi, Horishita Takafumi, Shiraishi Munehiro, Ueta Yoichi
Department of Anesthesiology, Jichi Medical University, Tochigi, Japan.
Pharmacology. 2007;79(4):236-42. doi: 10.1159/000101713. Epub 2007 Apr 13.
Neurons in the hypothalamus containing the neuropeptide orexin have been implicated in the control of sleep and wakefulness and in the pathology of narcolepsy. In this study, we investigated the effects of volatile anesthetics, ethanol and intravenous anesthetics on orexin-A-induced Ca2+-activated Cl- currents using Xenopus oocytes expressing orexin-1 receptors (OX1Rs). The volatile anesthetics isoflurane, enflurane and halothane inhibited Cl- currents elicited by 1-micromol/l orexin-A. Ethanol and the intravenous anesthetics pentobarbital and ketamine also inhibited the action of orexin-A. The inhibitory effects of all of the compounds tested were shown to be caused by the inhibition of OX1R function. These results may, at least in part, explain their hypnotic effects.
下丘脑中含有神经肽食欲素的神经元与睡眠和觉醒的控制以及发作性睡病的病理过程有关。在本研究中,我们使用表达食欲素-1受体(OX1Rs)的非洲爪蟾卵母细胞,研究了挥发性麻醉剂、乙醇和静脉麻醉剂对食欲素-A诱导的Ca2+激活Cl-电流的影响。挥发性麻醉剂异氟烷、恩氟烷和氟烷抑制了1微摩尔/升食欲素-A引发的Cl-电流。乙醇以及静脉麻醉剂戊巴比妥和氯胺酮也抑制了食欲素-A的作用。所有测试化合物的抑制作用均显示是由OX1R功能的抑制所致。这些结果可能至少部分地解释了它们的催眠作用。