Action of Halothane on Myocardial Adenylate Cyclase of Rat and Cat

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Abstract
The effect of halothane on myocardial adenylate cyclase was studied since c[cyclic]AMP is thought to participate in the regulation of myocardial contractility and since halothane has been shown to alter the activity of the cAMP-generating enzyme in other organs. Halothane significantly decreased the stimulatory effect of catecholamines on myocardial adenylate cyclase without altering the basal or the NaF-induced adenylate cyclase activity. In the presence of halothane (2%, vol/vol) the effect of 5 .mu.M norepinephrine on adenylate cyclase in rat myocardium, 74.0 .+-. 3.0, was reduced to 53.0 .+-. 3.0 pmol/mg protein per 5 min (P < 0.001) (control adenylate cyclase activity, 140.0 .+-. 1.0 pmol/mg protein per 5 min). The activation of adenylate cyclase by isoproterenol was also significantly decreased by halothane in rat and cat myocardium. The maximum stimulatory effect of isoproterenol (2.5 .mu.M) on adenylate cyclase in rat myocardium, 71.0 .+-. 8.0, was decreased to 26.0 .+-. 6.0 pmol/mg protein per 5 min (P < 0.001) in the presence of halothane (2%, vol/vol). Halothane diminished the effects of 5-guanylyl imidodiphosphate, which is thought to act at a site linking the regulatory and catalytic units of adenylate cyclase. The results suggest possible sites of halothane action on myocardial adenylate cyclase and raise the possibility that this inhibitory action of halothane and the decreased positive inotropic action of catecholamines in the presence of halothane may be related.

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