Regulation of beta-adrenoceptor number and subtype in 3T3-L1 preadipocytes by sodium butyrate.
In mouse 3T3-L1 preadipocytes, the glucocorticoid dexamethasone has been shown to promote a switch in beta-adrenoceptor subtype expression from beta 1 to beta 2 and to increase the total number of beta-adrenoceptors. The present study demonstrates that sodium butyrate also modulates beta-adrenoceptor expression in these cells. Incubation of preadipocytes with 2-10 mM butyrate for 24-48 h promoted a dose- and time-dependent switch in beta-adrenoceptor subtype from a near equal mixture of beta 1 and beta 2 to greater than 85% beta 2 and caused an approximate doubling of the receptor number. beta-Adrenoceptors were assayed in membranes prepared from 3T3-L1 cells using the radiolabeled antagonist [125I]iodocyanopindolol and the beta 2-selective antagonist ICI 118.551. Other short chain acids were not as effective as butyrate in promoting changes in beta-adrenoceptor expression. Cycloheximide (1.0 microgram/ml) inhibited the effects of butyrate on both beta-adrenoceptor subtype and number. Alterations in beta-adrenoceptor phenotype promoted by either butyrate or dexamethasone were functionally correlated with cAMP accumulation in these cells. Comparison of the effects of butyrate and dexamethasone on beta-adrenoceptor expression suggests that these two agents regulate beta-adrenoceptors by different mechanisms.
Stadel
J M
JM
Department of Molecular Pharmacology, Smith Kline and French Laboratories, Philadelphia, PA 19101.
Poksay
K S
KS
Nakada
M T
MT
Crooke
S T
ST
D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000378:metabolism; D007457:Iodine Radioisotopes; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D011863:Radioimmunoassay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
D002087:Butyrates; D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D020148:Butyric Acid; D003907:Dexamethasone; D003513:Cycloheximide; D000242:Cyclic AMP; D007545:Isoproterenol