Halothane, enflurane, and isoflurane do not affect the basal or agonist-stimulated activity of partially isolated soluble and particulate guanylyl cyclases of rat brain.
BACKGROUND
Evidence suggests that inhalational anesthetics interact with the nitric oxide-guanylyl cyclase signaling pathway in the central nervous system and that the inhibitation of this pathway in brain may result in an anesthetic, analgesic, or sedative effect. The mechanism of the effects inhalational anesthetics on this signaling pathway is not clear. This study attempted to determine whether inhalational anesthetics directly affect soluble or particulate guanylyl cyclase activity in a partially isolated enzyme system.


METHODS
The effects of halothane (0.44-4.4%), enflurane (1.34-6.7%), and isoflurane (0.6-5.0%) on basal or stimulated soluble or particulate guanylyl cyclase activity were examined. Soluble guanylyl cyclase was isolated from whole rat brain and was stimulated by sodium nitroprusside or nitric oxide. Particulate guanylyl cyclase was isolated from rat olfactory bulb and was stimulated by rat atrial natriuretic peptide(1-28). Cyclic guanosine monophosphate content was measured by radiommunoassay. The concentrations of anesthetics in the incubation solution were confirmed by gas chromatography methods.


RESULTS
None of the three anesthetics affected the activity of basal or stimulated soluble or particulate guanylyl cyclase at the concentrations examined in the current experimental conditions.


CONCLUSIONS
These results suggest that halothane, enflurane, and isoflurane do not directly interact with soluble or particulate guanylyl cyclases of rat brain.
Zuo
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Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Johns
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D000818:Animals; D001921:Brain / Q000201:enzymology*; D004737:Enflurane / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000378:metabolism*; D006221:Halothane / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D009599:Nitroprusside; D009569:Nitric Oxide; D004737:Enflurane; D007530:Isoflurane; D006162:Guanylate Cyclase; D006221:Halothane