Effects of dexamethasone on beta-adrenergic receptors in fetal lung explants.
The action of beta-adrenergic agonists on pulmonary surfactant secretion requires lung cell membrane beta-adrenergic receptors. In the fetus, the density of beta-adrenergic receptors in lung increases in the latter stages of gestation. The increase in density can also be induced by maternal glucocorticoid treatment. In this study, we measured beta-adrenergic receptors in developing rat lung by (-) [3H]-dehydroalprenalol (DHA) binding and confirmed the increase in beta-adrenergic receptors late in gestation. To determine if glucocorticoids have a direct effect on fetal lung to regulate beta-adrenergic receptors, we cultured fetal lung explants with dexamethasone. Treated explants had increased DHA binding compared with controls (138.0 +/- 8.8 versus 63.2 +/- 5.0 fmole/mg membrane protein). Scatchard analysis revealed that the increased DHA binding was due to an increase in maximum receptor number. There was also a significant difference in the dissociation constant of the treated and control explants (0.85 +/- 0.07 nM versus 0.43 +/- 0.08 nM, respectively; P less than 0.05), suggesting that the receptors induced by dexamethasone were of lower binding affinity. Cyclohexamide, an inhibitor of protein synthesis, completely eliminated the dexamethasone induced increase in DHA binding. These data indicate that glucocorticoids have a direct effect on fetal lung to increase beta-adrenergic receptor density and that new protein synthesis is required for this effect.
D000526:Alprenolol / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D003907:Dexamethasone / Q000494:pharmacology*; D005333:Fetus / Q000502:physiology; D006801:Humans; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011663:Pulmonary Surfactants; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D003907:Dexamethasone; D000526:Alprenolol