Biological maturation and β-adrenergic effectors: development of β-adrenergic receptors in rabbit heart
The β-adrenergic receptor, transduction processes and catalytic activity of the adenylate cyclase enzyme complex have been investigated in rabbit heart at different stages of biological maturation. The binding of [3H]-dihydroalprenolol to a washed membrane preparation isolated from rabbit ventricular muscle was used to characterize β-adrenergic receptors. Significant age-related differences were noted in β-receptor affinity (Kd) and density (RD) of neonatal and adult animals; the adult Kd was 3.7-fold greater and the RD 2-fold higher than the neonates. No significant differences in these parameters were detected among the 27-day old fetus and the 1- and 7-day old neonates. Age-dependent differences in agonist isoproterenol affinity for the receptor were not observed in contrast to the significant changes in antagonist (DHA) affinity.
Age-related changes in receptor affinity were also quantitated by determining the inhibitory potency of alprenolol on isoproterenol stimulated adenylate cyclase enzyme activity. A decreased affinity of the β-adrenergic receptor for alprenolol in the adult heart was indicated by a 3.7-fold greater Ki for the adult than the 1-day old neonate. Ontogenic variations in the coupling efficiency between the receptor and catalytic components of the adenylate cyclase complex were also evaluated. The Kd of the β-adrenergic receptor for isoproterenol and the EC50 for adenylate cyclase stimulation were determined under similar conditions. The corresponding coupling index (Kd/ EC50) was found to be 2.4-fold greater in the 1-day old neonate than adult, suggesting that for a given percentage increase in adenylate cyclase activity, a lower percentage of β-adrenergic receptor sites need be occupied in the neonate. These data extend previous studies (29) and indicate all components of the rabbit heart adenylate cyclase enzyme complex (i.e., the β-adrenergic receptor, the GTP-dependent transduction event, and the catalytic subunit) exhibit significant developmental changes.
KeywordsAdenylate Cyclase Receptor Density Adenylate Cyclase Activity Rabbit Heart Scatchard Analysis
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