Differential adrenergic regulation of beta 1- and beta 3-adrenoreceptor messenger ribonucleic acids in adipose tissues.
The levels of beta 1- and beta 3-adrenoreceptor mRNAs in several rat tissues were determined simultaneously with a sensitive nuclease protection assay. The beta 1-receptor gene was expressed to varying degrees in most tissues examined. By contrast, high levels of beta 3-receptor mRNA were only found in brown and white adipose tissues, indicating that beta 3-receptor gene expression is essentially adipose tissue specific. Surgical sympathectomy of interscapular brown adipose tissue increased beta 3-receptor mRNA levels by 2.4-fold, but did not affect beta 1-receptor mRNA levels. Exposure of rats to 4 C, which increases sympathetic nerve stimulation of IBAT, reduced beta 3-receptor mRNA levels in intact tissue but did not affect the denervation-induced increase in beta 3-receptor mRNA. Acute treatment of rats with norepinephrine greatly reduced beta 3 mRNA levels in both white and brown adipose tissues, but did not alter beta 1-receptor mRNA levels. These results indicate that beta 1- and beta 3-receptor mRNAs are differentially regulated and that norepinephrine released from sympathetic nerves is an important inhibitory regulator of beta 3-receptor mRNA levels. Injections of the beta-receptor agonist isoproterenol and the beta 3-receptor agonist BRL 26830 each reduced beta 3-receptor mRNA in brown and white fat, whereas injections of glucagon reduced beta 3-receptor mRNA in brown fat only. These data indicate that while stimulation of beta 3-receptors is sufficient to down-regulate beta 3 mRNA, other receptors that stimulate adenylyl cyclase have the same effect. Finally, the agonist-induced down-regulation of beta 3-receptor mRNA was associated with a reduction in beta 3-receptor activation of adenylyl cyclase in white adipose tissue.
Granneman
J G
JG
Department of Psychiatry, Wayne State University School of Medicine, Detroit, Michigan 48207.
Lahners
K N
KN
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D004983:Ethanolamines / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009638:Norepinephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000235:genetics* / Q000502:physiology
D004983:Ethanolamines; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; C057368:BRL 37344; D009638:Norepinephrine