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


CONCLUSIONS
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.
Miyawaki
I
I
Department of Anesthesia, Kyoto University Hospital, Japan.
Nakamura
K
K
Yokubol
B
B
Kitamura
R
R
Mori
K
K
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D006152:Cyclic GMP / Q000096:biosynthesis*; D003864:Depression, Chemical; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D008874:Midazolam / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D014665:Vasodilator Agents; D009599:Nitroprusside; D018698:Glutamic Acid; D016202:N-Methylaspartate; D007649:Ketamine; D006152:Cyclic GMP; D008874:Midazolam; D015742:Propofol