PROSTAGLANDIN-STIMULATED AND ISOPROTERENOL-STIMULATED CYCLIC-AMP ACCUMULATION IN RAT PERINATAL LUNG FIBROBLASTS - EFFECTS OF DEVELOPMENTAL AGE

Citation
Fj. Teixeira et al., PROSTAGLANDIN-STIMULATED AND ISOPROTERENOL-STIMULATED CYCLIC-AMP ACCUMULATION IN RAT PERINATAL LUNG FIBROBLASTS - EFFECTS OF DEVELOPMENTAL AGE, Pediatric research, 31(4), 1992, pp. 344-348
Citations number
31
Language
INGLESE
art.tipo
Article
Journal title
ISSN journal
0031-3998
Volume
31
Issue
4
Year of publication
1992
Part
1
Pages
344 - 348
Database
ISI
SICI code
0031-3998(1992)31:4<344:PAICA>2.0.ZU;2-J
Abstract
The fibroblast of the fetal and neonatal lung is intimately involved w ith lung development and function. Additionally, the perinatal rat lun g 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 effectiv eness of PG and the beta-adrenergic agonist, isoproterenol, and the de velopmental age sensitivity to these agonists on rat perinatal lung fi broblast cAMP accumulation. Confluent monolayer cultures of 3rd-passag e fibroblasts (> 95% purity) from d-3 newborn rats responded in a conc entration-dependent fashion to several PG (10(-8) - 10(-4) M) and isop roterenol (10(-7) - 2 x 10(-6) M) by increasing cAMP accumulation. The rank order of responsiveness, in terms of maximum accumulated cAMP, w ere carba PGI2 > PGE1 = PGI2 Na salt = PGI2 methyl ester much greater than PGE2 > isoproterenol. At the 3 developmental d tested [d 20) fetu s, 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/mu-g protein/15 m in at all three ages. On d 20 of gestation, the highest accumulation a chieved at the highest concentration tested was 30-70 fmol/mu-g protei n/15 min for each agonist. There was no age-dependent change in respon siveness to PGE2. Carba PGI2-stimulated cAMP accumulation increased fr om d 20 of gestation with each advancing age tested to approximately 1 5-fold by d 3 newborn. Isoproterenol stimulated a 2- to 3-fold increas e 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 i n perinatal rat lung fibroblasts the most prevalent endogenous PG, PGI 2 stimulates the greatest accumulation of cAMP, and this responsivenes s increases substantially with perinatal development. The implications in terms of lung development and function require resolution.