Decreased stimulatory guanosine triphosphate binding protein in dogs with pressure-overload left ventricular failure.
Alterations in the level and function of the stimulatory guanyl nucleotide binding protein (Gs) from the cardiac sarcolemma were examined in a canine model of heart failure. The present study is based on our previous investigations that demonstrated both a loss of beta-adrenergic agonist high-affinity binding sites and a decreased adenylate cyclase activity in sarcolemma from failing hearts. Using cholera toxin and [32P]NAD, we labeled the alpha subunit of Gs (Gs alpha) and found a 59% reduction in the level of this protein. Further, a 50% reduction in Gs activity was noted in a reconstitution assay utilizing membranes from the mouse S49 lymphoma cell line cyc-, which is deficient in Gs. These data suggest that, in this model of pressure-overload left ventricular failure, the acquired defect in the beta-adrenergic receptor/adenylate cyclase system involves a deficiency in the coupling protein Gs. Such an abnormality may explain the decreased adrenergic responsiveness of the failing left ventricle.
D000818:Animals; D002772:Cholera Toxin; D004195:Disease Models, Animal; D004285:Dogs; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics; D008561:Membrane Fusion; D009206:Myocardium / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism
D002772:Cholera Toxin; D019204:GTP-Binding Proteins