The FASEB Journal, Vol 7, 479-485, Copyright © 1993 by The Federation of American Societies for Experimental Biology

RESEARCH COMMUNICATIONS

Enflurane inhibits NMDA, AMPA, and kainate-induced currents in Xenopus oocytes expressing mouse and human brain mRNA

LH Lin, LL Chen and RA Harris
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.

Effects of enflurane, an inhalational anesthetic, on NMDA, AMPA, and kainate-gated currents were examined in Xenopus laevis oocytes expressing mouse or human brain mRNA. In oocytes expressing mouse mRNA, enflurane at an anesthetic concentration (1.8 mM) inhibited the NMDA-, AMPA-, and kainate-induced currents by 29-40%, 30-33%, and 20-27%, respectively, suggesting that all three glutamate ionotropic receptors are susceptible to suppression by inhalational anesthetics. Furthermore, inhibition by enflurane was independent of the concentrations of the agonists (NMDA, AMPA, and kainate) or the NMDA- coagonist (glycine). This suggests that enflurane inhibition does not result from a competitive interaction at glutamate or glycine binding sites. Enflurane also suppressed the oscillation and apparent desensitization of NMDA currents, suggesting an inhibition of Ca2+ influx through the NMDA channel. In oocytes expressing human brain mRNA, only kainate produced observable currents. Kainate currents of human channels were smaller in size than those of the mouse; however, the kainate concentration-response curve and percent inhibition (27- 29%) by enflurane were similar for mice and humans. The results suggest that human and mouse kainate receptors have similar pharmacological characteristics.

This article has been cited by other articles:

				J. Ogata, M. Shiraishi, T. Namba, C. T. Smothers, J. J. Woodward, and R. A. Harris Effects of Anesthetics on Mutant N-Methyl-D-Aspartate Receptors Expressed in Xenopus Oocytes J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 434 - 443. [Abstract] [Full Text] [PDF]

				E. I. Eger II, M. Liao, M. J. Laster, A. Won, J. Popovich, D. E. Raines, K. Solt, R. C. Dutton, F. V. Cobos II, and J. M. Sonner Contrasting Roles of the N-Methyl-d-Aspartate Receptor in the Production of Immobilization by Conventional and Aromatic Anesthetics. Anesth. Analg., May 1, 2006; 102(5): 1397 - 1406. [Abstract] [Full Text] [PDF]

				J. M. Sonner, J. F. Antognini, R. C. Dutton, P. Flood, A. T. Gray, R. A. Harris, G. E. Homanics, J. Kendig, B. Orser, D. E. Raines, et al. Inhaled Anesthetics and Immobility: Mechanisms, Mysteries, and Minimum Alveolar Anesthetic Concentration Anesth. Analg., September 1, 2003; 97(3): 718 - 740. [Abstract] [Full Text] [PDF]

				J. A. Campagna, K. W. Miller, and S. A. Forman Mechanisms of Actions of Inhaled Anesthetics N. Engl. J. Med., May 22, 2003; 348(21): 2110 - 2124. [Full Text] [PDF]

				A. Kitamura, W. Marszalec, J. Z. Yeh, and T. Narahashi Effects of Halothane and Propofol on Excitatory and Inhibitory Synaptic Transmission in Rat Cortical Neurons J. Pharmacol. Exp. Ther., January 1, 2003; 304(1): 162 - 171. [Abstract] [Full Text] [PDF]

				M. J. Rebecchi and S. N. Pentyala Anaesthetic actions on other targets:protein kinase C and guanine nucleotide-binding proteins Br. J. Anaesth., July 1, 2002; 89(1): 62 - 78. [Abstract] [Full Text] [PDF]

				K. M. Garrett and J. Gan Enhancement of gamma -Aminobutyric AcidA Receptor Activity by alpha -Chloralose J. Pharmacol. Exp. Ther., May 1, 1998; 285(2): 680 - 686. [Abstract] [Full Text]