Enflurane inhibits NMDA, AMPA, and kainate-induced currents in Xenopus oocytes expressing mouse and human brain mRNA.
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.
Lin
L H
LH
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Chen
L L
LL
Harris
R A
RA
D000368:Aged; D000818:Animals; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects*; D004737:Enflurane / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007051:Ibotenic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D007608:Kainic Acid / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000235:genetics; D013045:Species Specificity; D014982:Xenopus laevis; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D007473:Ion Channels; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D007051:Ibotenic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D004737:Enflurane; D007608:Kainic Acid; D002118:Calcium