Halothane Interaction with Guanine Nucleotide Binding Proteins in Mouse Heart

Volatile anesthetics have been shown to decrease hormone-induced adenosine cyclic monophosphate (cAMP) formation and to increase guanosine cyclic monophosphate (cGMP) content in mouse ventricular myocardium. Hormone-induced inhibition of adenylate cyclase, the enzyme that synthesizes cAMP, and the cGMP response to alpha adrenergic agonists are mediated by a guanine nucleotide binding protein (N) sensitive to pertussis toxin. To evaluate the involvement of N proteins in the action of halothane on cyclic nucleotides in the heart, mice were pretreated with pertussis toxin, 50 micrograms/kg, ip, 72 h prior to exposure to halothane, 1.2 vol%. Pretreatment with the toxin decreased the cGMP response to halothane by 65% but was without effect on the decrease in myocardial cAMP induced by the anesthetic. The results indicate that a functionally active pertussis toxin-sensitive N protein is involved in the cGMP response to halothane, but not in the cAMP response.