No functional atypical β-adrenergic receptors in human omental adipocytes

Abstract

Isoproterenol stimulates lipolysis in human omental adipocytes with an EC50 (concentration at which an agonist produces half-maximal stimulation) of 120 nM. CGP12177 (dl-4-3 [(1,1-dimethylethyl) amino]- 2-hydroxylpropoxy]1,3- dihydro-2H-benzimidazol-2-one hydrochloride), a potent β 1-β 2-adrenergic receptor (AR) antagonist but being an agonist for atypical β-AR, fails to stimulate lipolysis in these cells, even at a concentration as high as 0.1 mM. Since CGP12177 is a partial agonist, its failure to stimulate lipolysis may result from a poor stimulus-response coupling, so that it can not be excluded that atypical β-AR are actually present and even functional in these cells. To evaluate this hypothesis, we estimated the potency of CGP12177 to inhibit the isoproterenol-stimulated lipolysis. This inhibition curve reflects a single class of sites and the IC50- value (concentration at which an antagonist produces half-maximal inhibition) of CGP12177 (3.8 nM) is in good agreement with what should be expected for β1-AR/β2-AR. Moreover, metoprolol and atenolol, two β 1 - AR- selective antagonists, shift the isoproterenol dose-response curve to the right with high potency as well. These potencies are similar to the ones found for β1-AR in the human heart but appreciably higher than those which should be expected for atypical β-AR. The present study suggest that atypical β-AR are not functional in human omental adipocytes.