Publication: Suppression of cyclic guanosine monophosphate formation in rat cerebellar slices by propofol, ketamine and midazolam
Issued Date
1997-01-01
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ISSN
0832610X
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2-s2.0-0031417579
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Mahidol University
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SCOPUS
Bibliographic Citation
Canadian Journal of Anaesthesia. Vol.44, No.12 (1997), 1301-1307
Suggested Citation
Ikuko Miyawaki, Kumi Nakamura, Bencharatana Yokubol, Rie Kitamura, Kenjiro Mori Suppression of cyclic guanosine monophosphate formation in rat cerebellar slices by propofol, ketamine and midazolam. Canadian Journal of Anaesthesia. Vol.44, No.12 (1997), 1301-1307. doi:10.1007/BF03012780 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/18201
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Title
Suppression of cyclic guanosine monophosphate formation in rat cerebellar slices by propofol, ketamine and midazolam
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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 concentration-dependent 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.