Differential down-regulation of beta(3)-adrenergic receptor mRNA and signal transduction by cold exposure in brown adipose tissue of young and senescent rats

Diminished beta(3) adrenergic-stimulated thermogenesis in brown adipose tis sue (BAT) in senescent rats is restored by a short period of cold exposure. To investigate if the mechanism of this restoration involves preferential up-regulation of beta(3)-adrenergic signal transduction in senescent compar ed with young rats, we examined the steady state levels of beta(3)-adrenerg ic receptor messenger ribonucleic acid (beta(3)AR mRNA) and the dose/respon se relationship for the activation of adenylyl cyclase by the selective bet a(3)-adrenergic agonist, BRL 37344 in BAT membranes from young and senescen t rats with or without 2 days cold exposure at 8 degrees C, beta(3)AR mRNA declined by 30% with age and by 60% with cold exposure in young rats. In co ntrast, cold exposure did not down-regulate beta(3)AR mRNA in senescent rat s. BRL 37344-stimulated adenylyl cyclase activity was 38% less in senescent rats and was desensitized by cold exposure decreasing maximum stimulation by 78% and increasing, the dissociation constant 2.5-fold. Cold exposure de creased BRL 37344-stimulated adenylyl cyclase activity to a lesser extent i n senescent rats (50%), such that the activity was similar in cold-exposed young and old rats. These data indicate that although cold exposure did not , as we hypothesized, upregulate beta(3)-adrenergic signal transduction in the senescent rats, cold exposure preferentially down-regulated beta(3)AR m RNA and beta(3)AR-mediated adenylyl cyclase in the young compared with sene scent rats.