Effects of Anesthetics on tachykinin Receptors Expressed in Xenopus Oocytes

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The neuropeptide substance P (SP) and substance K(SK) modulate nociceptive transmission within the spinal cord. SPand SK are unique to a subpopulation of C-fibers found within primary afferent nerves. However, the effects of anesthetics on the substance P receptor (SPR) are not clear. In this study, we investigated the effects of volatile anesthetics and ethanol on SPR expressed in Xenopus oocytes. We examined the effects of halothane, isoflurane, enflurane, diethyl ether, and ethanol on SP-induced currents mediated by SPR expressed in Xenopus oocytes, using a whole-cell voltage clamp. All the volatile anesthetics tested and ethanol inhibited SPRinduced Ca^<2+>-activated C1^- currents at pharmacologically relevant concentrations. The protein kinase C (PKC) inhibitor bisindolylmaleimide I (GF109203X) enhanced the SP-induced CI^-currents. On the other hand, GF109203X abolished the inhibitory effects on SPR of the volatile anesthetics examined and of ethanol. These results demonstrate that halothane, isoflurane, enflurane, diethyl ether, and ethanol inhibit the function of SPR, and suggest that activation of PKC is involved in the mechanism of action of anesthetics and ethanol on the inhibitory effects of SPR.