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
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.