COMPARISON OF ATYPICAL BETA(3)-ADRENOCEPTOR AGONISTS WITH THEIR RESPECTIVE METABOLIC-ACTIVITIES IN RAT WHITE ADIPOCYTES

The metabolic activities of four types of beta(3)-adrenoceptor (AR) ag onists, BRL35135A, BRL28410, ICI215001 and CL316243, were compared wit h those of other beta(1)- and beta(2)-AR agonists in rat white adipocy tes. All the beta(3)-AR agonists caused cAMP formation, free fatty aci d release and 2-deoxyglucose uptake; the maximum activity levels were similar except for ICI215001, which was lower. However, the magnitude of potency and selectivity of these agonists differed. The most potent and selective beta(3)-agonist was CL316243. Metabolic activities and Northern blotting showed that there were three beta-AR subtypes that w ere coupled to adenylyl cyclase and contributed to the induction of li polysis and glucose uptake. The rank order of the amounts of beta-AR s ubtypes was beta(3) greater than or equal to beta(1)>beta(2). However, the physiological functions of beta-AR subtypes were essentially simi lar in rat white adipocytes. On the other hand, cAMP accumulation and Northern blotting showed that human adipocytes predominantly contained beta(2)-AR, with far lower levels of beta(1)- and beta(3)-ARs. These findings suggested that the beta(3)-AR plays an important role in ener gy metabolism and thermogenesis in which cross talk exists between bet a(1)- and beta(3)-ARs in rat adipocytes, while beta(2)-AR is the most important for the lipolysis regulation in human subcutaneous adipocyte s.