Inhibition of beta-adrenergic responsiveness in muscle cell cultures by dexamethasone.
Cultures of two myogenic cell lines, L6E9 and L8, were grown in the absence or presence of dexamethasone. Dexamethasone (1 microM) completely inhibited the formation of myotubes. Partial inhibition (20-40%) was obtained at a concentration as low as 1 nM. Dexamethasone also inhibited beta-adrenergic responsiveness, as noted by decreases in isoproterenol-stimulated adenylate cyclase activity and cAMP accumulation. These effects were both dose and time dependent. In the presence of dexamethasone, the number of beta-adrenergic receptors, as assessed by [125I]iodohydroxybenzylpindolol binding, decreased coordinately with the decrease in cAMP. A high affinity, limited capacity cytosolic binding site for [3H]triamcinolone acetonide observed under control conditions (Kd = 0.7 nM; maximum binding, 2.7 pmol/mg protein) increased in number as a function of developmental state. These data indicate that glucocorticoids inhibit myogenesis and beta-adrenergic responsiveness in vitro.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002459:Cell Fusion / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D007700:Kinetics; D009132:Muscles / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D014222:Triamcinolone Acetonide / Q000378:metabolism
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D011965:Receptors, Glucocorticoid; C011878:iodohydroxybenzylpindolol; D003907:Dexamethasone; D010869:Pindolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D014222:Triamcinolone Acetonide