Decreased beta-adrenergic responsiveness during senescence.
The capacity of the myocardium to respond to catecholamines is diminished in senescence. The intrinsic inotropic and chronotropic responses of the contractile elements to direct stimulation are unaltered with age, which suggests that the mechanism for diminished responsiveness lies in the sequence of events between the beta-adrenergic receptor and effector site. In a series of investigations of rat myocardial, rat lung, and human lymphocyte alpha- and beta-adrenergic function with age, it has been demonstrated that 1) there are no changes in either alpha 2- or beta-adrenergic receptor density or receptor antagonist affinity, 2) there is decreased beta-adrenergic receptor-agonist affinity with a corresponding decrease in the ability to form the high-affinity binding complex, 3) there is no change in alpha 2-adrenergic receptor agonist affinity, 4) there is decreased NaF- and hormone-stimulated adenylate cyclase activity, 5) there is decreased nucleotide regulatory protein function in the rat myocardium, 6) there is decreased catalytic unit function, and 7) there is decreased translocation of membrane-bound protein kinase. These changes in the beta-adrenergic stimulatory pathway may account for the diminished myocardial catecholamine responsiveness associated with aging.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000375:Aging; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology; D006321:Heart / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000378:metabolism; D009921:Metaproterenol / Q000494:pharmacology; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D009921:Metaproterenol; D011494:Protein Kinases; D000262:Adenylyl Cyclases; D007545:Isoproterenol