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

Abstract

The metabolic activities of four types of β3-adrenoceptor (AR) agonists, BRL35135A, BRL28410, ICI215001 and CL316243, were compared with those of other β1 and β2-AR agonists in rat white adipocytes. All the β3-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 β3-agonist was CL316243. Metabolic activities and Northern blotting showed that there were three β-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 β-AR subtypes was β3 ≫β1>β2. However, the physiological functions of β-AR subtypes were essentially similar in rat white adipocytes. On the other hand, cAMP accumulation and Northern blotting showed that human adipocytes predominantly contained β2-AR, with far lower levels of β1 and β3-ARs. These findings suggested that the β3AR plays an important role in energy metabolism and thermogenesis in which cross talk exists between β1 and β3-ARs in rat adipocytes, while β2-AR is the most important for the lipolysis regulation in human subcutaneous adipocytes.