Age-associated decrease in the catalytic unit activity of rat myocardial adenylate cyclase.

Abstract

Two techniques were employed to define the site of diminished adenylate cyclase activity observed in age-rat myocardium. We previously reported no change in beta-adrenergic receptor number or affinity but decreased NaF- and 5'-guanylylimidodiphosphate (GppNHp)-stimulated adenylate cyclase activity with age in the rat myocardium. These data suggest a defect in either N-protein or the catalytic unit component of adenylate cyclase. N-protein activity was assessed by the ability of myocardial membrane extracts from 3-, 12, and 24-month-old Fischer 344 rats to complement the N-protein deficient cyc- S49 mouse lymphoma cell line. Catalytic unit activity was assessed by the ability of forskolin to stimulate adenylate cyclase in myocardial membranes from young and old rats. The results demonstrate that both N-protein activity and catalytic unit activity are diminished with age in the rat myocardium. However, since N-protein is present in excess relative to catalytic unit, the data are consistent with the hypothesis that the loss of catalytic unit activity accounts for the loss of overall enzyme activity. The effect is tissue-specific, since erythrocyte membranes do not show the same age-dependent loss of adenylate cyclase activity.