This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Okamoto, T. Articles by Ueta, Y. Search for Related Content PubMed PubMed Citation Articles by Okamoto, T. Articles by Ueta, Y. Related Collections Mechanisms Pharmacology

---

ANESTHETIC PHARMACOLOGY

The Inhibitory Effects of Ketamine and Pentobarbital on Substance P Receptors Expressed in Xenopus Oocytes

Takashi Okamoto, MD^*, Kouichiro Minami, MD PhD^*, Yasuhito Uezono, MD PhD, Junichi Ogata, MD^*, Munehiro Shiraishi, MD^*, Akio Shigematsu, MD PhD^*, and Yoichi Ueta, MD PhD

Departments of *Anesthesiology and Physiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu; Department of Pharmacology, Nagasaki University, Graduate School of Biomedical Sciences, Japan

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

Substance P receptors (SPR) modulate nociceptive transmission within the spinal cord. The effects of IV anesthetics on SPR are not clear. In this study, we investigated the effects of IV anesthetics on SPR expressed in Xenopus oocytes. We examined the effects of ketamine, pentobarbital, propofol, and tramadol on SP-induced Ca²⁺-activated Cl^- currents mediated by SPR expressed in Xenopus oocytes using a whole-cell voltage clamp. Ketamine and pentobarbital inhibited the SPR-induced currents at pharmacologically relevant concentrations, but propofol and tramadol had little effect on the currents. We also studied the effects of ketamine and pentobarbital on [³H]-SP to SPR. Ketamine and pentobarbital inhibited the specific binding of [³H]-SP to SPR expressed in Xenopus oocytes. Scatchard analysis of [³H]-SP binding revealed that ketamine and pentobarbital decreased the apparent dissociation constant for binding and maximal binding, indicating noncompetitive inhibition. The protein kinase C (PKC) inhibitor bisindolylmaleimide I did not abolish the inhibitory effects of ketamine and pentobarbital on SP-induced Ca²⁺-activated Cl^- currents. The results suggest that ketamine and pentobarbital inhibit SPR function. The mechanism of their inhibition on SPR function could not be through activation of the PKC pathway and may be due to noncompetitive displacing the SP binding.

IMPLICATIONS: We investigated the effects of IV anesthetics on substance P receptors (SPR) expressed in Xenopus oocytes. Ketamine and pentobarbital inhibit SPR function via noncompetitive displacing SP binding. The findings imply that the inhibition of SPR function by these compounds may play a role in the analgesic effects of these IV anesthetics.

This article has been cited by other articles:

				Y. Shiga, K. Minami, K. Segawa, Y. Uezono, M. Shiraishi, T. Sata, C. Yamamoto, and K. Sung-Teh The Inhibition of Aortic Smooth Muscle Cell Proliferation by the Intravenous Anesthetic Ketamine Anesth. Analg., November 1, 2004; 99(5): 1408 - 1412. [Abstract] [Full Text] [PDF]