Comparison of Atypical β3-Adrenoceptor Agonists With Their Respective Metabolic Activities in Rat White Adipocytes

The metabolic activities of four types of beta3-adrenoceptor (AR) agonists, BRL35135A, BRL28410, ICI215001 and CL316243, were compared with those of other beta1- and beta2-AR agonists in rat white adipocytes. All the beta3-AR agonists caused cAMP formation, free fatty acid 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 beta3-agonist was CL316243. Metabolic activities and Northern blotting showed that there were three beta-AR subtypes that were coupled to adenylyl cyclase and contributed to the induction of lipolysis and glucose uptake. The rank order of the amounts of beta-AR subtypes was beta3 >>beta1> beta2. However, the physiological functions of beta-AR subtypes were essentially similar in rat white adipocytes. On the other hand, cAMP accumulation and Northern blotting showed that human adipocytes predominantly contained beta2-AR, with far lower levels of beta1- and beta3-ARs. These findings suggested that the beta3-AR plays an important role in energy metabolism and thermogenesis in which cross talk exists between beta1- and beta3-ARs in rat adipocytes, while beta2-AR is the most important for the lipolysis regulation in human subcutaneous adipocytes.