EFFECTS OF EXERCISE ON MYOCARDIAL ADENYLATE-CYCLASE AND GI-ALPHA EXPRESSION IN SENESCENCE

The present study investigated the influence of physical training on alterations leading to reduced adenosine 3',5'-cyclic monophosphate (cAMP) formation in aged myocardium. Senescent (28-mo-old) rats underwent a moderate treadmill exercise program and were compared with sedentary controls. In myocardial membranes from aged rats, isoprenaline-stimulated adenylate cyclase activity (AC) was reduced compared with that in young animals and was accompanied by an increase of pertussis toxin substrates (17.5%) and an increased amount of immunodetectable inhibitory guanine nucleotide-binding proteins (G(i)alpha; 72%). Physical training reduced the amount of G(i)alpha proteins (30-35%) in young and old animals and enhanced only isoprenaline-stimulated AC in the aged rats, and basal and 5'-guanylylimidodiphosphate [Gpp(NH)p]- as well as isoprenaline-stimulated AC in young rats. Physical training or aging had no effect on the number of beta-adrenoceptors or m-cholinoceptors or on forskolin-stimulated AC in either group. The amount of immunodetectable stimulatory guanine nucleotide-binding proteins (G(s)alpha) using an antiserum raised against the COOH-terminal peptide of G(s)alpha (RMHLRQYELL) was unchanged in either condition. It is concluded that enhanced G(i)alpha expression might be one mechanism leading to depressed cAMP formation in aged myocardium. Depressed AC and increased G(i)alpha can be partially reversed by physical training, especially in young myocardium. G(i)alpha might serve as a regulator of cardiac AC in a variety of physiological and pathophysiological situations in the absence of beta-adrenoceptor changes.