Abstract
Purpose
The nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system is involved in glutamatergic neurotransmission. The current study determined the effects of propofol, ketamine and midazolam on rat cerebellar cGMP formation, attempting to clarify whether the effect was due to suppression of NO-cGMP system or to direct interaction with glutamatergic receptors.
Methods
Cerebellar slices, obtained from six-to eight-day-old Wistar rats, were pretreated with propofol (10 μM–1 mM), ketamine (10–100 μM) or midazolam (1–100 μM) for 30 min. and then stimulated with L-glutamate (3 mM), N-methyl-D-aspartate (NMDA, 0.1 mM), kainate (0.1 mM) or sodium nitroprusside (SNP, 0.3 mM) (n = 5–11 for each group). The levels of cGMP were determined by radioimmunoassay.
Results
None of the anaesthetics studied altered cGMP levels when no stimulant was given. Propofol (10 μM–1 mM) suppressed L-glutamate-, NMDA-, kainate- and SNP stimulated cGMP formation in a concentrationdependent manner, the sensitivity to propofol was in the order of NMDA > kainate > L-glutamate, SNP Ketamine (10–100 μM) suppressed L-glutamate- and NMDA-stimulated cGMP formation, but did not suppress kainate-or SNP-stimulated cGMP formation. Midazolam (10–100 μM) did not affect NMDA-, L-glutamate-or SNP-stimulated cGMP formation, but suppressed kainate-induced formation.
Conclusion
The inhibitory effects of propofol, ketamine and midazolam on cGMP formation in rat cerebellar slices are due mainly to interaction with receptors for excitatory amines, and not due to the suppression of nitric oxide synthase or guanylate cyclase activities.
Résumé
Objectif
Le système monoxyde d’azote (NO)/monophosphate de guanosine cyclique (cGMP) participe à la neurotransmission glutamatergique. La présente étude recherchait l’influence du propofol, de la kétamine et du midazolam sur la formation cérébelleuse de cGMP en essayant de préciser si cette influence résultait de la suppression du système NO-cGMP ou d’une interaction directe avec les récepteurs glutamatergiques.
Méthodes
Des tranches de cerveau prélevées sur des rats Wistar âgés de six à huit jours ont été prétraitées avec du propofol (10 μm–1 mM), de la kétamine (10–100 μM) ou du midazolam (1–100 μM) et ensuite stimulées avec du L-glutamate (3 mM), du N-méthyl-D-aspartate (NMDA, 0,1 mM), du kainate (0,1 mM) ou du nitroprussiate de sodium (SNP 0,3 mM) (n = 5 pour chaque groupe). Le radio-immunodosage a servi à déterminer le niveau de cGMP
Résultats
En absence de stimulus, aucun des anesthésiques n’a modifié les niveaux de cGMP Le propofol (10 μM-mM) supprimait la formation de cGMP stimulée par le L-glutamate, le NMDA, le kainate et le SNP proportionnellement à la concentration. La sensibilité au propofol s’établissait dans l’ordre suivant NMDA > kainate > L-glutamate > SNP La kétamine (10–100 μM) supprimait la formation stimulée par le NMDA de L-glutamate et de cGMP mais ne supprimait pas la formation de cGMP stimulée par le kainate et le SNP Le midazolam (10–100 μM) n’affectait pas la formation de cGMP stimulée par le NMDA, le L-glutamate et le SNP mais supprimait la formation induite par le kainate.
Conclusion
Linfluence inhibitrice du propofol, de la kétamine et du midazolam sur la formation de cGMP dans les tranches cérébelleuses de rats est principalement causée par l’interaction des récepteurs des amines excitateurs et non par la suppression de la synthase du monoxyde d’azote ou à l’action de la guanylate cyclase.
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Supported in part by Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan, (No. 07457355) and Research Grant for Women from ESSO-Sckiyu, Japan. Presented in part at the Annual Meeting of the ASA, Atlanta, October 1995.
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Miyawaki, I., Nakamura, K., Yokubol, B. et al. Suppression of cyclic guanosine monophosphate formation in rat cerebellar slices by propofol, ketamine and midazolam. Can J Anaesth 44, 1301–1307 (1997). https://doi.org/10.1007/BF03012780
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DOI: https://doi.org/10.1007/BF03012780