Effects of prenatal terbutaline exposure on cellular development in lung and liver of neonatal rat: ornithine decarboxylase activity and macromolecules.
Endogenous beta-adrenergic input has been hypothesized to control patterns of cellular maturation in sympathetic target tissues by providing a timing signal for patterns of cell replication, differentiation, and responsiveness. In the current study, we examined the consequences of fetal exposure to a beta-agonist, terbutaline (2 or 10 mg/kg on gestational d 17, 18, and 19), in developing rat lung and liver, as assessed with ornithine decarboxylase activity and measurements of tissue macromolecules. Drug treatment caused an acute stimulation of ornithine decarboxylase in fetal and neonatal lung and blunted the peak of enzyme activity seen at 20-30 d postnatally without affecting acute responsiveness to beta-adrenergic stimulation (isoproterenol). Consistent with these results, patterns of cell replication and differentiation were altered, characterized by a deficit in cell acquisition (DNA content); in the tissue displaying fetal ODC stimulation (lung), there was also evidence for developmental abnormalities in RNA and protein. Thus, by prematurely stimulating beta-adrenergic receptors, prenatal administration of adrenergic agonists may have long-lasting, adverse effects on tissue development and responsiveness.
Kudlacz
E M
EM
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Navarro
H A
HA
Eylers
J P
JP
Lappi
S E
SE
Dobbins
S S
SS
Slotkin
T A
TA
D000818:Animals; D000831:Animals, Newborn; D004247:DNA / Q000378:metabolism; D005260:Female; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011297:Prenatal Exposure Delayed Effects; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats; D013726:Terbutaline / Q000494:pharmacology*
D011506:Proteins; D012313:RNA; D004247:DNA; D009955:Ornithine Decarboxylase; D013726:Terbutaline