Abstract
ABSTRACT: 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 β-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 (>95% purity) from d-3 newborn rats responded in a concentration-dependent fashion to several PG (10−8–10−4M) and isoproterenol (10−7–2 × 10−6 M) by increasing cAMP accumulation. The rank order of responsiveness, in terms of maximum accumulated cAMP, were carba PGI2 > PGE1 = PGI2 Na salt = PGI2 methyl ester ≫ PGE2 > 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/μg 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/μg 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. Isoproterenol stimulated a 2− to 3− fold increase in maximum cAMP accumulated between the d-20 fetus and d-1 newborn, but no further increase occurred at d 3. These data demonstrate that in perinatal rat lung fibroblasts the most prevalent endogenous PG, PGI2, stimulates the greatest accumulation of cAMP, and this responsiveness increases substantially with perinatal development. The implications in terms of lung development and function require resolution.
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Teixeira, F., Bevan, M. & Olson, D. Prostaglandin- and Isoproterenol-Stimulated Cyclic AMP Accumulation in Rat Perinatal Lung Fibroblasts: Effects of Developmental Age. Pediatr Res 31, 344–348 (1992). https://doi.org/10.1203/00006450-199204000-00008
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DOI: https://doi.org/10.1203/00006450-199204000-00008
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