Halothane inhibition of canine myocardial adenylate cyclase--modulation by endogenous factors.
We have hypothesized that the halothane-induced depression of myocardial contractility can be explained, at least in part, by halothane's depression of adenylate cyclase, previously demonstrated in whole homogenates of myocardial tissue. Canine myocardial sarcolemmal membranes, which contain the adenylate cyclase of myocardial cells, were separated from other cellular constituents. Halothane did not depress catecholamine-stimulated adenylate cyclase activity in this preparation. Reconstitution of the sarcolemmal membrane preparation with a 100,000 X g adenylate cyclase-free supernatant restored the depressant effect of halothane on adenylate cyclase stimulated by guanosine triphosphate (GTP) 100 microM alone (-55%, P less than 0.01) or in combination with l-isoproterenol 1 microM (-38%, P less than 0.05) or 2.5 microM (-40%, P less than 0.01). Dilution of the supernatant to half-strength decreased the magnitude of the halothane-induced depression of adenylate cyclase activity to 19% (P less than 0.01); at one-quarter dilution, the effect was no longer significant. This study demonstrates the presence of endogenous modulators of the action of halothane on canine myocardial adenylate cyclase that can be reversibly separated from the adenylate cyclase complex.
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D003470:Culture Media; D003864:Depression, Chemical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006160:Guanosine Triphosphate / Q000502:physiology; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000201:enzymology; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000201:enzymology*; D012508:Sarcolemma / Q000201:enzymology
D000067956:Adenylyl Cyclase Inhibitors; D003470:Culture Media; D006160:Guanosine Triphosphate; D007545:Isoproterenol; D006221:Halothane