Control of adenylate cyclase activity in developing rat heart and liver: effects of prenatal exposure to terbutaline or dexamethasone.
Adrenergic stimulation and glucocorticoids have been hypothesized to control the development of beta-adrenergic receptors and responsiveness. In the current study, rats were exposed to a beta-agonist (terbutaline) or a glucocorticoid (dexamethasone) during late gestation, and the development of adenylate cyclase activity and beta-receptor binding was evaluated in membranes prepared from the heart and liver. In control heart, basal, isoproterenol-stimulated and forskolin-stimulated adenylate cyclase showed distinct developmental spikes of activity that were unrelated to changes in receptor binding sites, but that instead corresponded temporally to periods of sympathetic neuronal activation. Prenatal exposure to terbutaline initially enhanced all three enzymatic measures in the immediate postpartum period but delayed the appearance and exaggerated the magnitude of the subsequent peaks; again, these changes occurred without specific relation to effects on receptor binding. Dexamethasone produced a similar shift in the peaks of cardiac enzyme activity. In the liver, where beta-adrenergic receptors and responsiveness decline after birth, terbutaline and dexamethasone had much smaller effects on adenylate cyclase. These results suggest that beta-adrenergic stimulation serves as a trophic factor controlling the ontogenetic rise of adenylate cyclase activity; regulation involves the level of the enzyme itself rather than changes in receptor binding capabilities or receptor-specific linkages. Consequently, prenatal administration of beta-agonists or glucocorticoids can cause long-term alterations in enzyme activity and responsiveness.
Navarro
H A
HA
Department of Pharmacology, Duke University Medical Center, Durham, N.C.
Kudlacz
E M
EM
Slotkin
T A
TA
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D005576:Colforsin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000196:embryology / Q000254:growth & development*; D007545:Isoproterenol / Q000494:pharmacology; D008099:Liver / Q000196:embryology / Q000201:enzymology / Q000254:growth & development*; D009206:Myocardium / Q000201:enzymology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013726:Terbutaline / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D003907:Dexamethasone; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D013726:Terbutaline