Overexpression of alpha 2-adrenergic receptors in fetal rat heart: receptors in search of a function.
alpha 2-Adrenergic receptors are transiently overexpressed by many types of developing cells. In the current study, the developmental profile and cellular function of these receptors were examined in the fetal and neonatal rat heart. alpha 2-Receptors, assessed with [3H]rauwolscine binding, were extremely high in fetal hearts on gestational day 19, 30-fold higher than values seen in adults. Receptor binding decreased by two-thirds by gestational day 21 and dropped by half again by postnatal day 3. To assess potential cellular functions controlled by the alpha 2-receptors, the capability of an alpha 2-agonist (clonidine) to inhibit membrane-associated adenylate cyclase activity was measured in three different settings: basal enzyme activity, the enzymatic response to isoproterenol (dependent upon beta-receptor linkages to the regulatory protein, Gs), and the response to forskolin (independent of receptor-Gs interactions). Despite the high number of alpha 2-receptors in fetal hearts, clonidine failed to alter any of the adenylate cyclase activity measures. In light of the postulated role of alpha 2-receptors in the maintenance of fetal/neonatal atrioventricular conduction, the excess alpha 2-receptors are probably linked to other cellular events, such as movement of calcium into the cell.
Lin
W
W
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Seidler
F J
FJ
McCook
E C
EC
Slotkin
T A
TA
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D003000:Clonidine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D005318:Fetal Heart / Q000378:metabolism*; D005865:Gestational Age; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D015016:Yohimbine / Q000378:metabolism
D011942:Receptors, Adrenergic, alpha; D005576:Colforsin; D015016:Yohimbine; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D003000:Clonidine