Phosphatidic acid phosphatase in neonatal rat lung: effects of prenatal dexamethasone or terbutaline treatment on basal activity and on responsiveness to beta adrenergic stimulation.
Phosphatidic acid phosphatase (PAPase) is a key enzyme in the synthesis of lung surfactant. This study compares the effects of prenatal exposure (gestational days 17, 18 and 19) to two drugs which enhance surfactant synthesis: dexamethasone (0.2 mg/kg) and terbutaline (2 or 10 mg/kg). Maternal dexamethasone treatment did not cause an initial stimulation of lung PAPase but did eventually evoke a small increase after the 1st postnatal week. The effect was selective in that brain PAPase activity was generally unaffected; liver PAPase was stimulated during the early neonatal period only. Dexamethasone also prolonged the developmental period of peak reactivity of lung PAPase to beta developmental period of peak reactivity of lung PAPase to beta adrenergic stimulation (tested with acute isoproterenol challenge), which ordinarily accompanies genesis of alveoli in the 2nd to 3rd postnatal week. Significant growth retardation was present even at this low dose of dexamethasone. In contrast, maternal administration of the beta adrenergic agonist, terbutaline, resulted in a large increase in basal enzyme activity in the lung during the immediate perinatal period and enhanced the responsiveness to isoproterenol challenge. The effect of terbutaline was accompanied by little or no growth impairment. Thus, although prenatal administration of either glucocorticoids or beta adrenergic agonists can enhance lung PAPase activity and reactivity to stimulation, the two classes of drugs differ substantially in time course of effect and in the propensity to retard growth.
Kudlacz
E M
EM
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina.
Navarro
H A
HA
Slotkin
T A
TA
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000201:enzymology; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D008168:Lung / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D008431:Maternal-Fetal Exchange; D009929:Organ Size / Q000187:drug effects; D010711:Phosphatidate Phosphatase / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D012016:Reference Values; D013726:Terbutaline / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D003907:Dexamethasone; D010744:Phosphoric Monoester Hydrolases; D010711:Phosphatidate Phosphatase; D013726:Terbutaline