Dose-dependent effect of prenatal dexamethasone treatment on beta-adrenergic receptor coupling to ornithine decarboxylase and cyclic AMP.
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. We 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.
Bian
X P
XP
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Seidler
F J
FJ
Bartolome
J
J
Kavlock
R J
RJ
Bartolome
M
M
Slotkin
T A
TA
D000375:Aging / Q000187:drug effects*; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D008137:Longitudinal Studies; D008431:Maternal-Fetal Exchange; D009206:Myocardium / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D003907:Dexamethasone; D000242:Cyclic AMP; D009955:Ornithine Decarboxylase; D007545:Isoproterenol