Role of beta(1)- and beta(3)-adrenoceptors in the regulation of lipolysis and thermogenesis in rat brown adipocytes

To evaluate the physiological functions of beta(1)-, beta(2)-, and beta(3)-adrenoceptors (ARs) in brown adipose tissue, the Lipolytic and respiratory effects of various adrenergic agonists and antagonists mere studied in rat brown adipocytes. The beta-agonists stimulated both lipolysis and respiration (8-10 times above basal levels), with the following order of potency (concentration eliciting 50% of maximum response): CL-316243 (beta(3))> BRL-37344 (beta(3)) > isoproterenol (mainly beta(1)/beta(2)) > norepinephrine (NE; mainly beta(1)/beta(2)) > epinephrine (mainly beta(1)/beta(2)) much greater than dobutamine (beta(1)) much greater than procaterol (beta(2)) Schild plot coefficients of competitive inhibition experiments using ICI-89406 (beta(1) antagonist) revealed that more than one type of receptor mediates NE action. It is concluded from our results that 1) NE, at low plasma levels (1-25 nM), stimulates lipolysis and respiration mainly through beta(1)-ARs, 2) NE, at higher levels, stimulates lipolysis and respiration via both beta(1)- and beta(3)-ARs, 3) beta(2)-ARs play only a minor role, and 4) beta(3)-ARs may represent the physiological receptors for the high NE concentrations in the synaptic cleft; where the high-affinity beta(1)-ARs are presumably desensitized. It is also suggested that lipolysis represents the flux-generating step regulating mitochondrial respiration.