||Dose-Dependent Effect of Prenatal Dexamethasone Treatment on beta-Adrenergic Receptor Coupling to Ornithine Decarboxylase and Cyclic AMP.
Bian, X. P. ;
Seidler, F. J. ;
Bartolome, J. ;
Kavlock, R. J. ;
Bartolome, M. ;
||Duke Univ. Medical Center, Durham, NC. Dept. of Pharmacology.;Health Effects Research Lab., Research Triangle Park, NC.;Public Health Service, Rockville, MD.
||EPA-R-813769 ;PHS-HD-09713; EPA/600/J-90/523;
Beta adrenergic receptors ;
Adenosine cyclic monophosphate ;
Ornithine decarboxylase ;
Animal pregnancy ;
Dose-response relationships ;
||Some EPA libraries have a fiche copy filed under the call number shown.
||Glucocorticoids regulate the coupling of beta-adrenergic receptors to cell function. In the current study, the potential role of these agents in the development of adrenergic responses was evaluated in the offspring of pregnant rats given 0.8 mg/kg of dexamethasone on gestational days 17, 18 and 19. The authors examined the postnatal development of beta-receptors coupling to ornithine decarboxylase in heart and kidney throughout neonatal life into young adulthood; this enzyme is involved in transduction of neural signals controlling cellular replication and differentiation. Dexamethasone exposure perturbed the basal pattern of cardiac ornithine decarboxylase activity and attenuated the response of the enzyme in both heart and kidney to acute challenge with the beta-agonist, isoproterenol. Subsensitivity persisted into the postweaning period. This dosage regimen of dexamethasone also suppressed renal cyclic AMP responses to isoproterenol, but exposure to a lower dose (0.2 mg/kg) enhanced the response. Thus, although low doses of glucocorticoids foster development of the coupling of beta-receptors to cellular transduction mechanisms, higher doses such as those used to stimulate lung function may lastingly obtund adrenergic sensitivity.
||Pub. in Jnl. of Developmental Physiology, v14 p125-130 Dec 90. Sponsored by Health Effects Research Lab., Research Triangle Park, NC., and Public Health Service, Rockville, MD.
|NTIS Title Notes
||Reprint: Dose-Dependent Effect of Prenatal Dexamethasone Treatment on beta-Adrenergic Receptor Coupling to Ornithine Decarboxylase and Cyclic AMP.
||57Q; 57B; 57Y
||PC A02/MF A01