Evidence for a functional β3‐adrenoceptor in man

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Abstract
1 The existence of a functional β3-adrenoceptor in man was investigated by studying the lipolytic action of selective β-adrenoceptor agents in isolated white omental and subcutaneous fat cells. 2 The non-selective β1/β2-adrenoceptor antagonist, CGP 12177 was lipolytic in both omental and subcutaneous fat cells. The intrinsic activity relative to isoprenaline was greater in omental than in subcutaneous cells. 3 Addition of the β2-adrenoceptor antagonist, ICI 118,551 and the β1-adrenoceptor antagonist CGP20712A in combination or the non-selective β-adrenoceptor antagonist propranolol alone (all 10−7 m), induced a rightward shift of the dose-response curves for isoprenaline- and BRL37344-stimulated lipolysis of about 4 and 2 log-units, respectively. However, the antagonists did not alter lipolysis induced by CGP12177. 4 Several concentrations of β-adrenoceptor antagonists were used to determine the pA2 values by Schild analysis. The values for CGP 20712A and ICI 118,551 (6.63 ± 0.20 and 6.25 ± 0.12) as antagonists of the lipolytic effects of CGP 12177 were over 2 units lower than the pA2 value for CGP 20712A against the response to the selective β1-agonist dobutamine (8.58 ± 0.23) and the pA2 value for ICI 118,551 against the response to the selective β2-agonist terbutaline (9.15 ± 0.26). 5 β3-Adrenoceptor mRNA expression, investigated with a polymerase chain reaction assay, was demonstrated in both types of adipocytes in the same cell preparations that had a lipolytic response to CGP 12177. 6 In conclusion, human white fat cells express an atypical β-adrenoceptor in addition to β1- and β2-adrenoceptors. This receptor is stimulated more selectively by the β1-/β2-antagonist CGP 12177 than by BRL 37344 and is poorly sensitive to blockade by selective β1- and β2-antagonists. On the basis of the pharmacological properties and the mRNA analyses, we suggest that this atypical receptor corresponds to the β3-adrenoceptor subtype.