Arotinolol is a weak partial agonist on beta 3-adrenergic receptors in brown adipocytes.
Arotinolol, a clinically used alpha/beta-adrenergic blocker, has been demonstrated to be an anti-obesity agent. The anti-obesity effect of arotinolol was suggested to be the result of direct activation of thermogenesis in brown-fat cells. We tested the ability of arotinolol to stimulate thermogenesis (oxygen consumption) in isolated brown-fat cells and in intact animals. Arotinolol stimulated thermogenesis in brown-fat cells isolated from mouse and hamster. A relatively low sensitivity to the beta-adrenergic antagonist propranolol (pK(B) approximately 6) indicated that arotinolol interacted with the beta3-adrenergic receptor. On the beta3-receptor, arotinolol was a very weak (EC50 approximately 20 microM) and only partial (approximately 50%) agonist, but arotinolol also demonstrated the properties of being a beta3-receptor antagonist with a pK(B) of 5.7. In intact animals, only the antagonistic action of arotinolol could be observed. Because arotinolol is only a very weak and partial agonist on the beta3-receptors, direct stimulation of thermogenesis in brown adipose tissue is unlikely to be sufficient to cause significant weight loss. It may be necessary to invoke additional pathways to explain the anti-obesity effects of chronic treatment with arotinolol.
Zhao
J
J
The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, Sweden.
Golozoubova
V
V
Cannon
B
B
Nedergaard
J
J
D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000502:physiology*; D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005260:Female; D006358:Hot Temperature; D008297:Male; D008647:Mesocricetus; D051379:Mice; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D022702:Receptors, Adrenergic, beta-3 / Q000502:physiology
D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D022702:Receptors, Adrenergic, beta-3; C024523:arotinolol