Differential down-regulation of beta3-adrenergic receptor mRNA and signal transduction by cold exposure in brown adipose tissue of young and senescent rats.

Diminished beta3 adrenergic-stimulated thermogenesis in brown adipose tissue (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 beta3-adrenergic signal transduction in senescent compared with young rats, we examined the steady state levels of beta3-adrenergic receptor messenger ribonucleic acid (beta3AR mRNA) and the dose/response relationship for the activation of adenylyl cyclase by the selective beta3-adrenergic agonist, BRL 37344 in BAT membranes from young and senescent rats with or without 2 days cold exposure at 8 degrees C. beta3AR mRNA declined by 30% with age and by 60% with cold exposure in young rats. In contrast, cold exposure did not down-regulate beta3AR mRNA in senescent rats. 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 decreased BRL 37344-stimulated adenylyl cyclase activity to a lesser extent in 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, up-regulate beta3-adrenergic signal transduction in the senescent rats, cold exposure preferentially down-regulated beta3AR mRNA and beta3AR-mediated adenylyl cyclase in the young compared with senescent rats.