Effects of fetal dexamethasone exposure on postnatal control of cardiac adenylate cyclase: beta-adrenergic receptor coupling to Gs regulatory protein.
In the adult, glucocorticoids have been shown to upregulate beta-adrenergic control of adenylate cyclase by a variety of mechanisms; glucocorticoids are also thought to play a role in development of cardiac adrenergic function. In the current study, pregnant rats were given 0.2 mg/kg of dexamethasone on gestational days 17, 18, and 19 and the effects on the development of cardiac beta-receptors and their linkage to the stimulatory G-protein, Gs, were examined at 4 days postpartum. beta-Receptor numbers and affinity were unaffected by dexamethasone exposure, nor was there any change in the ability of the GTP analog, Gpp(NH)p, to shift the affinity state of the receptor. Addition of Gpp(NH)p to cardiac membranes enhanced basal and isoproterenol-stimulated adenylate cyclase activity, but the total response to isoproterenol, with or without Gpp(NH)p, represented a very small fraction of total enzymatic activity. Quantitative analysis of Gs indicated no changes attributable to dexamethasone treatment. Although prenatal dexamethasone has been shown to increase adenylate cyclase reactivity to beta-adrenergic input, the effect appears to be at the level of the catalytic subunit of adenylate cyclase, rather than at receptor or G-protein stages.
Bian
X
X
Department of Pharmacology, Duke University Medical Center/VA Medical Center, Durham, NC 27710.
Seidler
F J
FJ
Olsen
C
C
Raymond
J R
JR
Slotkin
T A
TA
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003907:Dexamethasone / Q000633:toxicity*; D004789:Enzyme Activation; D005260:Female; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000201:enzymology; D010869:Pindolol / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D013723:Teratogens / Q000633:toxicity*
D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D013723:Teratogens; D003907:Dexamethasone; D010869:Pindolol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol