Regulation of postnatal beta-adrenergic receptor/adenylate cyclase development by prenatal agonist stimulation and steroids: alterations in rat kidney and lung after exposure to terbutaline or dexamethasone.
Glucorticoids and adrenergic stimulation are both thought to control the development of beta-adrenergic receptors/responses. In the current study, rats were exposed to dexamethasone or terbutaline during late gestation and the development of beta-receptor binding capabilities and adenylate cyclase activity evaluated in membrane preparations from kidney and lung. Prenatal dexamethasone exposure produced postnatal adrenergic hyperreactivity of kidney adenylate cyclase; the effect resulted from increases in the enzyme itself, as both basal adenylate cyclase and forskolin-stimulation of the enzyme were also increased by dexamethasone. Similarly, prenatal terbutaline exposure evoked increases in basal, isoproterenol-stimulated and forskolin-stimulated adenylate cyclase in the kidney. In the lung, dexamethasone produced an initial postnatal deficit in basal adenylate cyclase and deficient responsiveness to isoproterenol, but the deficit resolved shortly after birth. Terbutaline selectively promoted the ability of isoproterenol to stimulate lung adenylate cyclase in the first few days after birth, without alterations in basal adenylate cyclase; this was followed by a period of prolonged subsensitivity of both basal and isoproterenol-stimulated activity. Although dexamethasone and terbutaline also caused significant changes in development of beta-receptor binding capabilities, in neither tissue could these effects account for the direction or magnitude of the changes in adenylate cyclase reactivity. Thus, glucocorticoids and beta-agonists can participate in the programming of development of postsynaptic reactivity by exerting actions upon post-receptor coupling mechanisms.
Kudlacz
E M
EM
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Navarro
H A
HA
Kavlock
R J
RJ
Slotkin
T A
TA
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000375:Aging / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013726:Terbutaline / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D003907:Dexamethasone; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D013726:Terbutaline