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

Abstract

Suppression of cyclic guanosine monophosphate formation in rat cerebellar slices by propofol, ketamine and midazolamPu_,lxme: The nitric oxide (NO)/c),clic guanosine monophosphate (cGMP) system is involved in glutamatergic neurotransmlssion. 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<GMP system or to direct interaction with glutamatersic receptors. ~o~:Cerebellar slices, obtained from six-to eight-day-old Wistar rats, were pretreated with propofol ( I 0//M--I mM), ketamine ( I 0-100/aM) or midazolam (I-100/aM) for 30 min. and then stimulated with L-glutamate (3 mM), N-meth)A-D-aspartate (NMDA, O. I mM), kainate (0. I mM) or sodium nitroprusside (SNP, 0.3 mM) (n = 5-1 I for each group). The levels of cGMP were determined by radioimmunoassay. :]Rema~13: None of the anaesthetics studied altered cGMP levels when no stimulant was given. Propofol (I 0/aM-I mlVl) 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/aM) suppressed L-glutamate-and NMDA-stimulated cGMP formation, but did not suppress kainate-or SNP-stimulated cGMP formation. Midazolam (10-100/aM) 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 s)mthase or guanylate cyclase activities.

Intravenous Anesthetic, Propofol Affects Synaptic Responses in Cerebellar Purkinje Cells

“…Compared to other cellular preparation, the relatively higher concentrations of propofol are required to produce effects in brain slice preparation. 17 , 27 , 28) …”

Implications of the suppression of guanylate cyclase activity by halothane

“…In another study of ours using rat cerebellar slices [6], halothane, at concentrations that suppressed the formation of cGMP induced by N-methyl daspartate (NMDA) and d-aspartate, did not alter the effects induced by SNP. Masaki and Kondo suspected that the concentration of SNP we used (0.3 mM) was a supramaximal one [1], but under our experimental conditions, SNP continued to increase cGMP levels in a concentration-dependent manner at least up to 10 mM [7]. Moreover, both d-aspartate (1 mM) and SNP (0.3 mM) increased cGMP to similar levels, and halothane suppressed only the increase induced by daspartate [6].…”

Methylene blue treatment for vasoplegia and resultant isoelectric processed EEG (Bispectral Index)

“…The ability of methylene blue to inhibit the production of NO may provide some insight into its mechanism of action. Nitric oxide is a known neuromodulator with activity in the CNS [26,27]; a reduction in NOS activity decreases MAC [28,29] and propofol requirements [30] in animals. These interactions may be complex, as volatile anesthetics also decrease NOS activity [31].…”