Expression of adenylyl cyclase subtypes in brown adipose tissue: neural regulation of type III

Previous work has shown that neural stimulation of brown adipose tissue (BAT) increases norepinephrine-stimulated adenylyl cyclase (AC) activity 2- to 3-fold by a mechanism involving postreceptor alterations of the AC system. In view of the recent discovery of multiple AC subtypes, the purposes of this study were to determine which of these subtypes are present in BAT and to examine whether their expression is altered by neural stimulation. Direct hybridization and polymerase chain reaction analyses demonstrated that BAT expresses messenger RNAs (mRNAs) encoding AC-III, AC-IV, AC-V, and AC-VI subtypes. Of the subtypes detected in BAT, neural stimulation increased only AC-III mRNA levels. Activation of beta-adrenergic receptors was sufficient to increase AC-III mRNA levels; however, the potency of beta-receptor agonists was greatly enhanced by simultaneous stimulation of alpha 1-adrenergic receptors. The close correlation between the increases in AC activity and the induction of AC-III mRNA across various physiological and pharmacological treatments indicates that this subtype is responsible for the increase in AC activity that occurs after adrenergic stimulation.