Enflurane-induced release of an excitatory amino acid, glutamate, from mouse brain synaptosomes.
To clarify the mechanisms of enflurane-induced convulsions, we examined the effects of enflurane, halothane, and diethyl ether on the release of an excitatory neurotransmitter, glutamate, from isolated pinched-off nerve terminals (synaptosomes) of the mouse cerebral cortex. At concentrations corresponding to those used clinically (0.75 and 1.25 mM), enflurane released more glutamate than did halothane. Diethyl ether (10 and 58 mM) had no effect on glutamate release. Enflurane (0.75-15 mM) increased glutamate and aspartate release in a dose-dependent manner but had little effect on the release of the inhibitory neurotransmitters glycine and gamma-aminobutyric acid or on the release of glutamine. A glutamate uptake inhibitor, kainic acid (1 mM), did not affect enflurane-induced glutamate release. Replacement of the medium's Ca2+ by Co2+, or exposure to cold (about 2 degrees C), suppressed the enflurane-induced glutamate release. Depolarization caused by 40 mM K+ increased the basal level of glutamate released, and enflurane-induced glutamate release was lower after depolarization. Enflurane had no effect in synaptosomes prepared from the cerebellum, diencephalon and pons, or medulla oblongata. Thus, enflurane increased Ca(2+)- and temperature-dependent glutamate release, especially from synaptosomes of the cerebral cortex. These data provide a pathophysiologic explanation for enflurane-induced convulsions.
Hirose
T
T
Department of Anesthesiology, Kansai Medical University, Osaka, Japan.
Inoue
M
M
Uchida
M
M
Inagaki
C
C
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004737:Enflurane / Q000494:pharmacology*; D004986:Ether / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D006221:Halothane / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
D005971:Glutamates; D004986:Ether; D004737:Enflurane; D006221:Halothane