Biological maturation and beta-adrenergic effectors: pre- and postnatal development of the adenylate cyclase system in the rabbit heart

The relationship between biological maturation and adenylate cyclase activity was studied in membrane preparations of rabbit ventricular muscle. Basal adenylate cyclase activity was lower in the adult than in the 1-day-old neonate or 27-day-old fetus. Maximal stimulation of adenylate cyclase by isoproterenol was 2.5 times greater and the EC50 values were 2-fold higher in the adult than the 27-day-old fetus or 1-, 7- and 12-day-old neonate. No significant differences in isoproterenol- or Mg++-stimulated activity were observed among the younger age groups nor was the Mg++-stimulated Vmax of adenylate cyclase significantly affected by biological maturation. Sodium fluoride, guanyl-5'yl imidodiphosphate and GTP also stimulated adenylate cyclase activity in a dose-dependent fashion similar to isoproterenol. Sodium fluoride (2.5-10 mM) increased adenylate cyclase activity in the adult to a significantly greater extent than the 1-day-old neonate. Guanyl-5'yl imidodiphosphate and GTP (0.1-10.0 microM) augmented adenylate cyclase activity to approximately the same degree (although some small differences were observed) in the fetus, neonate and adult. However, when guanyl-5'yl imidodiphosphate was preincubated with membrane preparations before in vitro assay, adenylate cyclase activity was increased 10-fold in the adult, whereas membranes from 1-day-old animals were unaffected. These data suggest that the processes regulating hormonal and pharmacological activation of adenylate cyclase are modified during biological maturation.