Abstract: | To evaluate the physiological functions of 1-, 2-, and 3-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 (mainly 1/ 2) > norepinephrine (NE; mainly 1/ 2) > epinephrine (mainly 1/ 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 both 1- and 3-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-affinity 1-ARs are presumablydesensitized. It is also suggested that lipolysis represents theflux-generating step regulating mitochondrial respiration. |