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Am J Physiol Cell Physiol 273: C1136-C1142, 1997;
0363-6143/97 $5.00
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Vol. 273, Issue 4, C1136-C1142, October 1997

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

Claude Atgié, François D'Allaire, and Ludwik J. Bukowiecki

Department of Physiology, Faculty of Medicine, Laval University, Quebec, Quebec, Canada G1K 7P4

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 were 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) >>  dobutamine (beta 1) >>  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.

brown adipose tissue; brown fat; respiration; beta 2-adrenoceptors; norepinephrine; epinephrine; sympathetic nervous system


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