ONTOGENY OF ATRIAL-NATRIURETIC-FACTOR RECEPTORS AND CYCLIC-GMP RESPONSE IN RABBIT RENAL GLOMERULI

Atrial natriuretic factor (ANF) has been identified in fetal and newborn mammals, and considerable data regarding fetal ANF metabolism are available. However, there is limited information concerning ANF receptors or receptor ontogenesis in developing mammals. We measured ANF receptor binding capacity, affinity, and ANF-induced cyclic GMP (cGMP) generation in isolated renal glomeruli from fetal (29 d gestation, term = 31 d), newborn (3 d), juvenile (28 d), and adult rabbits. The (mean +/- SEM) glomerular receptor binding capacity values for ANF in fetal and newborn animals (10 +/- 1 and 12 +/- 3 fmol/mg protein) were similar and significantly lower than the values for juvenile and adult animals (30 +/- 8 and 74 +/- 15 fmol/mg protein, respectively). In contrast, there were no significant differences in ANF receptor affinity values or dose-dependent increases in ANF-stimulated cGMP generation among the age groups studied. In competition studies, we observed effective displacement of I-125-ANF by C-ANF4-23, a ring-deleted ANF analogue, in adult, juvenile, and newborn glomeruli; however, C-ANF displaced only about 50% of the I-125-ANF in fetal tissue. The addition of C-ANF did not elicit cGMP generation, nor did C-ANF affect ANF-induced cGMP generation in fetal, newborn, or adult glomeruli. These results indicate that 1) the ANF receptor-guanylate cyclase system is intact in 29-d fetal rabbit glomeruli, and 2) the ANF-induced cGMP formation is similar in fetal and adult animals, whereas receptor binding capacity is relatively higher in adult glomeruli. These results suggest a higher proportion of nonguanylate cyclase-coupled ANF receptors in the mature rabbit.