Forskolin-stimulated adenylate cyclase activity in fetal and adult rabbit myocardial membranes.

It has previously been reported that there is an increase in the concentration of myocardial beta-adrenergic receptors as well as an increase in the sensitivity of adenylate cyclase stimulation by L-isoproterenol in fetal rabbit myocardial membranes from 21 to 31 days' gestation. To investigate whether a change in the catalytic component of the beta-adrenergic receptor-adenylate cyclase complex is responsible for the observed increase in adenylate cyclase activity, I have measured the latter in the presence of forskolin and manganese chloride, compounds that can directly stimulate the catalytic component. Myocardial membranes were obtained from fetal rabbits at 21, 28, and 31 days' gestation and from pregnant adult animals. There was an increase in basal adenylate cyclase activity from the fetal to the adult stage. The percent of maximal stimulation by L-isoproterenol in fetuses from 21 through 28 to 31 days' gestation and in the adult animal. However, although forskolin was the most potent stimulator of adenylate cyclase, the degree of stimulation was equivalent in all groups tested. Similar results were obtained with manganese chloride. We conclude that the catalytic component of the beta-adrenergic receptor-adenylate cyclase complex in myocardial membranes is stimulated to an equivalent degree at all gestational ages in fetal and adult rabbits and shows no maturational changes.