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 immunoassay 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.
Masaki
E
E
Department of Pharmacology (I), Jikei University School of Medicine, Tokyo, Japan. jkyakuri@sepia.onc.ne.jp
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002248:Carbon Monoxide / Q000494:pharmacology*; D006152:Cyclic GMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D002248:Carbon Monoxide; D007530:Isoflurane; D006162:Guanylate Cyclase; D006152:Cyclic GMP