Cell-specific down-regulation of the beta 3-adrenergic receptor.
Previous studies have shown that beta 3-adrenergic receptors, in contrast to the beta 1 and beta 2 subtypes, do not undergo desensitization following short term activation (minutes) with agonists. Longer activation (hours) has been shown to induce desensitization of the beta 3-adrenergic receptor in some, but not all, cases, suggesting that cell- or species-specific mechanisms may be involved. We investigated the contribution of the cell type to the pattern of beta 3-adrenergic receptor long term desensitization by studying, in parallel, two cell lines (Chinese hamster fibroblasts and murine Ltk- cells) expressing the human beta 3-adrenergic receptor. Sustained agonist-promoted down-regulation of the beta 3-adrenergic receptor could be induced in Ltk- cells, whereas only a transient and weak reduction of receptor number was observed in Chinese hamster fibroblasts. The half-life of the beta 3-adrenergic receptor was not affected by the agonist activation in either cell line, indicating that in contrast to the beta 2-adrenergic receptor, degradation of preexisting receptor protein does not contribute to down-regulation. Sustained reduction of receptor RNA levels, monitored by reverse transcriptase polymerase chain reaction, was exclusively shown in Ltk- cells and probably accounted for most of the observed down-regulation. Differences in the ability of the receptor to stimulate adenylyl cyclase activity in the two cell lines may be responsible for the distinct patterns of beta 3-adrenergic receptor down-regulation.
Nantel
F
F
Département de Biochimie, Université de Montréal, Québec, Canada.
Marullo
S
S
Krief
S
S
Strosberg
A D
AD
Bouvier
M
M
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation; D006207:Half-Life; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3
D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol