No functional atypical beta-adrenergic receptors in human omental adipocytes.
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 beta 1-/beta 2- adrenergic receptor (AR) antagonist but being an agonist for atypical beta-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 beta-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 beta 1-AR/beta 2-AR. Moreover, metoprolol and atenolol, two beta 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 beta 1-AR in the human heart but appreciably higher than those which should be expected for atypical beta-AR. The present study suggest that atypical beta-AR are not functional in human omental adipocytes.
Van Liefde
I
I
Department of Protein Chemistry, Free University Brussels (V.U.B), St. Genesius-Rode, Belgium.
Van Ermen
A
A
Vauquelin
G
G
D000273:Adipose Tissue / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects; D009852:Omentum; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000032:analysis*
D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; C033394:CGP 12177