Effects of Anesthetics on the Function of Orexin-1 Receptors Expressed in Xenopus Oocytes

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Abstract
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.