DIFFERENTIAL ADRENERGIC REGULATION OF BETA-1-ADRENOCEPTOR AND BETA-3-ADRENOCEPTOR 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.