ROLE OF BETA(1)-ADRENOCEPTOR AND BETA(3)-ADRENOCEPTOR IN THE REGULATION OF LIPOLYSIS AND THERMOGENESIS IN RAT BROWN ADIPOCYTES

To evaluate the physiological functions of beta(1)-, beta(2)-, and bet a(3)-adrenoceptors (ARs) in brown adipose tissue, the Lipolytic and re spiratory effects of various adrenergic agonists and antagonists mere studied in rat brown adipocytes. The beta-agonists stimulated both lip olysis and respiration (8-10 times above basal levels), with the follo wing order of potency (concentration eliciting 50% of maximum response ): CL-316243 (beta(3))> BRL-37344 (beta(3)) > isoproterenol (mainly be ta(1)/beta(2)) > norepinephrine (NE; mainly beta(1)/beta(2)) > epineph rine (mainly beta(1)/beta(2)) much greater than dobutamine (beta(1)) m uch greater than procaterol (beta(2)) Schild plot coefficients of comp etitive inhibition experiments using ICI-89406 (beta(1) antagonist) re vealed that more than one type of receptor mediates NE action. It is c oncluded 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) be ta(3)-ARs may represent the physiological receptors for the high NE co ncentrations in the synaptic cleft; where the high-affinity beta(1)-AR s are presumably desensitized. It is also suggested that lipolysis rep resents the flux-generating step regulating mitochondrial respiration.