h-89 and 2-deoxyglucose-6-phosphate

The beta(3)-adrenoceptor agonist, (RR+SS)-(+/-)-4-[2-)2-)3-chlorophenyl)-2-hydroxyethyl)amino)propyl]ph enoxyacetate (BRL37344), stimulated fuel utilisation by isolated mouse soleus muscle at concentrations 10- to 100-fold lower than those required to stimulate lipolysis in brown adipocytes. At 1x10(-10) M BRL37344, uptake and phosphorylation of 2-deoxyglucose was increased (40%), as was glucose-oxidation (50%), palmitate-oxidation (70%) and oxidation of [2-14C]pyruvate (2-fold), indicating stimulation of tricarboxylic acid cycle reactions. Oxidation of [1-14C]pyruvate was unaffected, indicating no stimulation of pyruvate dehydrogenase activity. Other beta(3)-adrenoceptor agonists, disodium(RR)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]- 1,3-benzodioxazole-2,2-dicarboxylate (CL316,243, 1x10(-7) M) and (S)-4-¿2-[2-hydroxy-3-(4-hydroxyphenoxy)propylamino]ethyl¿pheno xymeth ylcyclohexylphosphiric acid lithium salt (SB226552, 1x10(-9) M), achieved similar stimulation of 2-deoxyglucose uptake and phosphorylation but (+/-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one (CGP12177A) had no effect. The inhibitor of protein kinase A, H-89 (isoquinolinesulfonamide), had little effect on the stimulation of pyruvate-oxidation by BRL37344, while the specific inhibitor of protein kinase C, bisindolylmaleimide IX, reduced the stimulated rate to slightly below basal values. We consider that these responses provide evidence of the presence of a novel beta-adrenoceptor in skeletal muscle, which we have termed beta(skel)-adrenoceptor.

Topics: Adrenergic beta-Agonists; Animals; Carbon Dioxide; Carbon Radioisotopes; Citric Acid Cycle; Deoxyglucose; Dose-Response Relationship, Drug; Enzyme Inhibitors; Ethanolamines; Glucose; Glucose-6-Phosphate; In Vitro Techniques; Indoles; Isoquinolines; Mice; Mice, Obese; Muscle, Skeletal; Oxidation-Reduction; Palmitates; Phosphorylation; Propanolamines; Protein Kinase C; Pyruvic Acid; Sulfonamides