Arotinolol is a weak partial agonist on β3-adrenergic receptors in brown adipocytes
| Autor: | Jin Zhao, Valeria Golozoubova, Barbara Cannon, Jan Nedergaard |
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| Rok vydání: | 2001 |
| Předmět: | |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 79:585-593 |
| ISSN: | 1205-7541 0008-4212 |
| DOI: | 10.1139/y01-027 |
| Popis: | Arotinolol, a clinically used α/β-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 β-adrenergic antagonist propranolol (pKB [Formula: see text] 6) indicated that arotinolol interacted with the β3-adrenergic receptor. On the β3-receptor, arotinolol was a very weak (EC50 [Formula: see text] 20 µM) and only partial ([Formula: see text]50 %) agonist, but arotinolol also demonstrated the properties of being a β3-receptor antagonist with a pKB 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 β3-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.Key words: arotinolol, β3-adrenergic receptor, brown adipose tissue, thermogenesis, mouse, hamster, rat. |
| Databáze: | OpenAIRE |
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