Developmental alterations in guanine nucleotide regulation of the beta-adrenergic receptor-adenylate cyclase system of skeletal muscle.
The postnatal development of skeletal muscle is accompanied by an increased capacity for glycogenolysis and anaerobic glycolysis. In the present study, regulatory features of cAMP synthesis were examined in neonatal and adult rabbit sarcolemmal membranes. Adult sarcolemma exhibited a 3-, 6-, and 10-fold greater adenylate cyclase activity than neonate for basal, NaF, and isoproterenol plus GTP, respectively. The Km for activation by isoproterenol was 1.4 X 10(-8) M and 6 X 10(-8) M for GTP. The number of beta-receptors was similar (0.9-1.2 pmol/mg). 10 microM GTP shifted isoproterenol EC50 from 1 X 10(-8) M to 1 X 10(-7) M in adult; neonatal agonist affinity was unaffected by GTP. Cholera toxin stimulated adenylate cyclase activity 2-fold and catalyzed 32P ribosylation of a Mr = 42,000 peptide in adult sarcolemma; both activities were low or absent in neonate. Isoproterenol-stimulated GTPase activity was elevated 4-fold in adult compared to neonatal sarcolemma. Mn2+ ion-stimulated basal activity, an indicator of catalytic function of adenylate cyclase, was also elevated in adult. Together, these findings suggest that the development of catecholamine-sensitive cAMP synthesis in muscle is governed by the coordinate expression of the regulatory and catalytic proteins of adenylate cyclase, but not the beta-receptor.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004082:Dihydroalprenolol / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000494:pharmacology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D024510:Muscle Development; D009132:Muscles / Q000378:metabolism*; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012969:Sodium Fluoride / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D006165:Guanylyl Imidodiphosphate; D004082:Dihydroalprenolol; D006160:Guanosine Triphosphate; D012969:Sodium Fluoride; D002772:Cholera Toxin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol