BRL37344, but not CGP12177, stimulates fuel oxidation by soleus muscle in vitro

The beta(3)-adrenoceptor agonist, (RR + SS)-(+/-)-4-[2-)2-)3-chlorophenyl)- 2-hydroxyethyl)amino)propyl]phenoxyacetate (BRL37344), stimulated fuel util isation by isolated mouse soleus muscle at concentrations 10- to 100-fold l ower than those required to stimulate lipolysis in brown adipocytes. At 1 X 10(-10) M BRL37344, uptake and phosphorylation of 2-deoxyglucose was incre ased (40%), as was glucose-oxidation (50%), palmitate-oxidation (70%) and o xidation of [2-C-14]pyruvate (2-fold), indicating stimulation of tricarboxy lic acid cycle reactions. Oxidation of [1-C-14]pyruvate was unaffected, ind icating no stimulation of pyruvate dehydrogenase activity. Other beta(3)-ad renoceptor agonists, disodium(RR)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl] -amino]propyl]-1,3-benzodioxazole-2,2-dicarboxylate (CL316,243, 1 X 10(-7) M) and (S)-4-{2-[2-hydroxy-3-(4-hydroxyphenoxy)propylamino]ethyl]phenoxymet hylcyclohexylphosphiric acid lithium salt (3B226552, 1 X 10(-9) M), achieve d similar stimulation of 2-deoxyglucose uptake and phosphorylation but (+/- )-4-(3-t-buty- lamino-2-hydroxypropoxy)benzimidazol-2-one (CGP12177A) had n o effect. The inhibitor of protein kinase A, H-89 (isoquinolinesulfonamide) , had little effect on the stimulation of pyruvate-oxidation by BRL37344, w hile the specific inhibitor of protein kinase C, bisindolylmaleimide IX, re duced the stimulated rate to slightly below basal values. We consider that these responses provide evidence of the presence of a novel beta-adrenocept or in skeletal muscle, which we have termed beta(skel)-adrenoceptor. (C) 20 00 Elsevier Science B.V. All rights reserved.