Effect of halothane on rat liver adenylate cyclase: role of cytosol components.
Halothane, in a number of tissues, alters the activity of adenylate cyclase, the enzyme that catalyzes the formation of cyclic 3',5'-adenosine monophosphate, an important intracellular regulator. The present studies demonstrate that in rat liver whole homogenates, basal and glucagon-stimulated adenylate cyclase activity is increased by halothane. In isolated rat liver membranes, halothane does not increase basal activity and it decreases activity stimulated by glucagon. Suspension of membranes in the cytosol fraction restores the halothane-induced increase of basal and glucagon-stimulated activity. When cytosol denatured by trypsin or heat was used, the halothane-induced increase in glucagon-stimulated activity was lost, but the increase of basal activity was still observed. Suspension of membranes in albumin solution restored the effect of halothane on basal activity only. These results suggest that presence of heat-labile proteins in the cytosol fraction that modulate the halothane interaction with rat liver adenylate cyclase.
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology*; D006358:Hot Temperature; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D011489:Protein Denaturation; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014357:Trypsin
D000067956:Adenylyl Cyclase Inhibitors; D012710:Serum Albumin, Bovine; D006160:Guanosine Triphosphate; D005934:Glucagon; D014357:Trypsin; D000262:Adenylyl Cyclases; D006221:Halothane