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Canadian Journal of Anesthesia, Vol 44, 1301-1307, Copyright © 1997 by Canadian Anesthesiologists' Society


ARTICLES

Suppression of cyclic guanosine monophosphate formation in rat cerebellar slices by propofol, ketamine and midazolam

I Miyawaki, K Nakamura, B Yokubol, R Kitamura and K Mori
Department of Anesthesia, Kyoto University Hospital, Japan.

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 microM-1 mM), ketamine (10-100 microM) or midazolam (1-100 microM) 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 microM-1 mM) suppressed L-glutamate-, NMDA-, kainate- and SNP stimulated cGMP formation in a concentration-dependent manner, the sensitivity to propofol was in the order of NMDA > kainate > L-glutamate. SNP. Ketamine (10-100 microM) suppressed L-glutamate- and NMDA-stimulated cGMP formation, but did not suppress kainate- or SNP-stimulated cGMP formation. Midazolam (10-100 microM) 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.


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Anesth. Analg.Home page
T. Yasuda, S. Takahashi, and A. Matsuki
Tumor Necrosis Factor-{alpha} Reduces Ketamine- and Propofol-Induced Anesthesia Time in Rats
Anesth. Analg., October 1, 2002; 95(4): 952 - 955.
[Abstract] [Full Text] [PDF]




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Copyright © 1997 by the Canadian Anesthesiologists' Society.