Role of beta 1- and beta 3-adrenoceptors in the regulation of lipolysis and thermogenesis in rat brown adipocytes |
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Authors: | Atgie, Claude D'Allaire, Francois Bukowiecki, Ludwik J. |
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Abstract: | To evaluate the physiological functions of1-,2-, and3-adrenoceptors (ARs) in brownadipose tissue, the lipolytic and respiratory effects of variousadrenergic agonists and antagonists were studied in rat brownadipocytes. The -agonists stimulated both lipolysis and respiration(8-10 times above basal levels), with the following order ofpotency (concentration eliciting 50% of maximum response):CL-316243 (3) > BRL-37344(3) > isoproterenol (mainly1/2) > norepinephrine (NE; mainly1/2) > epinephrine (mainly1/2) dobutamine (1) procaterol (2). Schild plot coefficients of competitive inhibition experiments using ICI-89406 (1 antagonist) revealed thatmore than one type of receptor mediates NE action. It is concluded fromour results that 1) NE, at low plasma levels (1-25 nM), stimulates lipolysis and respiration mainly through 1-ARs,2) NE, at higher levels, stimulateslipolysis and respiration via both1- and3-ARs,3)2-ARs play only a minor role,and 4)3-ARs may represent thephysiological receptors for the high NE concentrations in the synapticcleft, where the high-affinity1-ARs are presumablydesensitized. It is also suggested that lipolysis represents theflux-generating step regulating mitochondrial respiration. |
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