An adipose tissue-specific beta-adrenergic receptor. Molecular cloning and down-regulation in obesity.
Clones encoding an atypical beta-adrenergic receptor were isolated from a rat brown adipose tissue cDNA library. This receptor expressed in Chinese hamster ovary (CHO) cells displays a low affinity for beta-adrenergic antagonists and a high affinity for BRL 37344, an agonist that selectively stimulates lipolysis in adipose tissue. The rank order of potency for agonist-mediated increases in intracellular cAMP in transfected cells correlates with that for agonist-mediated stimulation of lipolysis in brown adipocytes. Northern blot analysis demonstrates that this receptor subtype is expressed only in brown and white adipose tissue where it represents the predominant beta-receptor subtype. The amount of atypical beta-adrenergic receptor present in adipose tissue of obese (fa/fa) Zucker rats is reduced by up to 71% as compared with lean (Fa/Fa) control animals. These findings suggest that a change in the expression of this beta-adrenergic receptor subtype may play a role in obesity.
Muzzin
P
P
Departement de Biochimie Medicale, Centre Medical Universitaire, Geneve, Switzerland.
Revelli
J P
JP
Kuhne
F
F
Gocayne
J D
JD
McCombie
W R
WR
Venter
J C
JC
Giacobino
J P
JP
Fraser
C M
CM
D002001:Adipose Tissue, Brown / Q000502:physiology* / Q000503:physiopathology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D004247:DNA / Q000235:genetics; D015536:Down-Regulation; D015723:Gene Library; D006801:Humans; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D009765:Obesity / Q000503:physiopathology*; D011061:Poly A / Q000235:genetics; D012313:RNA / Q000235:genetics; D012333:RNA, Messenger; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D011061:Poly A; D012313:RNA; D004247:DNA