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ANESTHETIC PHARMACOLOGY

The Inhibitory Effects of Anesthetics and Ethanol on Substance P Receptors Expressed in Xenopus Oocytes

Kouichiro Minami, MD PhD^*, Munehiro Shiraishi, MD^*, Yasuhito Uezono, MD PhD, Susumu Ueno, MD PhD, and Akio Shigematsu, MD PhD^*

Departments of *Anesthesiology and Pharmacology, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan; and Second Department of Pharmacology, Nagasaki University School of Medicine, Nagasaki, Japan

Address correspondence and reprint requests to Kouichiro Minami, MD, PhD, Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu, Fukuoka 807-8555, Japan. Address e-mail to kminami{at}med.uoeh-u.ac.jp

The neuropeptide substance P (SP) modulates nociceptive transmission within the spinal cord. SP is unique to a subpopulation of C fibers found within primary afferent nerves. However, the effects of anesthetics on the SP 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, by using a whole-cell voltage clamp. All the volatile anesthetics tested, and ethanol, inhibited SPR-induced Ca²⁺-activated Cl^- currents at pharmacologically relevant concentrations. The protein kinase C inhibitor bisindolylmaleimide I (bisindolylmaleimide) enhanced the SP-induced Cl^- currents. However, bisindolylmaleimide 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 protein kinase C is involved in the mechanism of action of anesthetics and ethanol on the inhibitory effects of SPR.

IMPLICATIONS: We examined the effects of halothane, isoflurane, enflurane, diethyl ether, and ethanol on substance P receptor (SPR) expressed in Xenopus oocytes, by using a whole-cell voltage clamp. All the anesthetics and ethanol inhibited SPR function, and the protein kinase C (PKC) inhibitor abolished these inhibitions. These results suggest that anesthetics and ethanol inhibit SPR function via PKC.

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