title: The beta-adrenergic radioligand [3H]CGP-12177, generally classified as an antagonist, is a thermogenic agonist in brown adipose tissue.
abstract: The effect of CGP-12177, originally developed as a radioligand with antagonist properties for binding studies of beta-adrenergic receptors, was investigated in brown adipose tissue. Contrary to expectations, CGP-12177 showed clear agonist properties in experiments with hamster brown-fat cells, with a maximal effect in stimulating oxygen consumption similar to that of the physiological stimulator noradrenaline, and also with a potency similar to that of noradrenaline [EC50 (50% effective concn.) approx. 70 nM]. This value could be contrasted with the very high affinity of CGP-12177 (KD about 1 nM) for ligand-binding sites on the cells. It is therefore suggested that the high-affinity binding site may not be the one that mediates the CGP-12177-stimulated thermogenesis in isolated cells. Also, when injected into cold-adapted rats, CGP-12177 stimulated non-shivering thermogenesis similarly to noradrenaline. This observation, in conjunction with the reported low general sympathomimetic effect of CGP-12177, may indicate that CGP-12177 could be of interest for the development of anti-obesity drugs.
authors.affiliation: Wenner-Gren Institute, University of Stockholm, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Mohell
authors.forename: A
authors.initials: A
authors.lastname: Dicker
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D006224:Cricetinae; D008024:Ligands; D008647:Mesocricetus; D010101:Oxygen Consumption / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*
chemical_list: D000319:Adrenergic beta-Antagonists; D008024:Ligands; D011412:Propanolamines; C033394:CGP 12177