The epinephrine-sensitive adenylate cyclase of rat liver plasma membranes. Role of guanyl nucleotides.
The epinephrine sensitivity in vitro of the adenylate cyclase system in liver plasma membranes from adrenalectomized rats was increased by the addition of 1 to 100 muM GTP or GDP in the incubation medium. Basal and glucagon-stimulated cyclase activities were also enhanced by GTP and GDP. These effects occurred even in the absence of an ATP-regenerating system. They were mimicked by 5'-guanyl diphosphonate and a series of guanyl derivatives, indicating that the structural requirement for the GTP action is not very stringent. Guanyl nucleotides did not increase the affinity of the adenylate cyclase system for the activating hormones, nor did they protect the enzyme activity against denaturation. Their synergic effect was due to an enhancement of the affinity of the enzyme for the substrate MgATP and also to an increase of the maximal velocity of the reaction. It is proposed that the guanyl nucleotides act directly and primarily upon the catalytic component of the cyclase system, independently of their effects on the binding of the activating hormones to liver plasma membrane. Since the activating effects of epinephrine and glucagon are similar in the presence of GTP, but not in its absence, it is suggested that the lower efficiency of epinephrine under normal conditions is not due to intrinsic membrane characteristics, but rather, to superimposed extraneous modulations.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D005459:Fluorides / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008274:Magnesium / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D006150:Guanine Nucleotides; D006160:Guanosine Triphosphate; D005934:Glucagon; D000262:Adenylyl Cyclases; D008274:Magnesium; D005459:Fluorides; D004837:Epinephrine