Halogenated volatile anesthetics inhibit carbon monoxide-stimulated soluble guanylyl cyclase activity in rat brain

Background: Because of halogen contents, halogenated volatile anesthetics (HVA) have a similarity to nitric oxide (NO) in terms of great affinity for the ferrous ion. Interactions between HVA and NO at the ferrous ion of soluble guanylyl cyclase (sGC) have been reported in different tissues. Carbon monoxide (CO), a more stable gas than NO, activates sGC by the same mechanism as NO. This study was undertaken to examine the effect of HVA on CO-stimulated sGC activity in rat brain. Methods: Sprague-Dawley rat brain was homogenized and ultracentrifuged. The resulting supernatant was used as sGC fraction. The fraction was incubated with CO and HVA, and the activity of sGC was determined by measuring cyclic guanosine monophosphate (cGMP) production using an enzyme immuno-assay in aliquots of the supernatant. Results: CO clearly increased cGMP production in a dose- dependent manner. Sevoflurane and isoflurane produced significant and dose- dependent inhibition of CO-stimulated sGC activity. There was no difference in the inhibitory effect between the two anesthetics. GTP dose-dependently increased CO-stimulated cGMP production. Both anesthetics decreased GTP production, but the inhibition by the anesthetics was not significant at higher GTP concentrations. Conclusions: These results suggest that HVA can compete with CO at the ferrous ion of sGC and inhibit the activity of this enzyme.