Prostaglandin- and isoproterenol-stimulated cyclic AMP accumulation in rat perinatal lung fibroblasts: effects of developmental age.

The fibroblast of the fetal and neonatal lung is intimately involved with lung development and function. Additionally, the perinatal rat lung fibroblast is a significant source of prostaglandins (PG) I2 and E2, which in turn affect lung development and function. Their effects may be mediated by cAMP. We, therefore, tested both the relative effectiveness of PG and the beta-adrenergic agonist, isoproterenol, and the developmental age sensitivity to these agonists on rat perinatal lung fibroblast cAMP accumulation. Confluent monolayer cultures of 3rd-passage fibroblasts (greater than 95% purity) from d-3 newborn rats responded in a concentration-dependent fashion to several PG (10(-8)-10(-4) M) and isoproterenol (10(-7)-2 x 10(-6) M) by increasing cAMP accumulation. The rank order of responsiveness, in terms of maximum accumulated cAMP, were carba PGI2 greater than PGE1 = PGI2 Na salt = PGI2 methyl ester much greater than PGE2 greater than isoproterenol. At the 3 developmental d tested [d 20 fetus, d 1 newborn, and d 3 newborn (term = d 22)], PGE2, carba PGI2, and isoproterenol each elicited concentration-dependent increases in cAMP accumulation. Unstimulated cAMP levels were 2-5 fmol/micrograms protein/15 min at all three ages. On d 20 of gestation, the highest accumulation achieved at the highest concentration tested was 30-70 fmol/micrograms protein/15 min for each agonist. There was no age-dependent change in responsiveness to PGE2. Carba PGI2-stimulated cAMP accumulation increased from d 20 of gestation with each advancing age tested to approximately 15-fold by d 3 newborn.(ABSTRACT TRUNCATED AT 250 WORDS)