caa a22 4500 475833368 CHVBK 20180406123847.0 cr unu---uuuuu 170329e20001201xx s 000 0 eng 10.1023/A:1007838125152 doi (NATIONALLICENCE)springer-10.1023/A:1007838125152 Role of β-Adrenergic Receptor Subtypes in Lipolysis [Elektronische Daten] [Simon Louis, Graham Jackman, Tracy Nero, Dimitri Iakovidis, William Louis] In vitro lipolysis stimulated by low (-)-isopre-naline concentrations (≤30 nM) in epididymal white adipo-cytes from Sprague-Dawley rats was inhibited at least 60-80% by the specific β1-antagonists LK 204-545 and CGP 20712A (1 μM), suggesting that at these low (10 nM) concentrations of (-)-isoprenaline lipolysis was primarily (80%) but not solely mediated via β1-adrenergic receptors. Low concentrations (100 nM) of (-)-noradrenaline and formoterol also confirmed a role for β1-adrenergic receptors in mediating lipolysis at low concentrations of these agonists. At higher agonist concentrations, β3-adrenergic receptors were fully activated and were the dominant β-adrenergic receptor subtype mediating the maximum lipolytic response, and the maximum response was not affected by the β1-antagonists, demonstrating that the β3-receptor is capable of inducing maximum lipolysis on its own. Studies of lipolysis induced by the relatively β2-selective agonist formoterol in the presence of β1-blockade (1 μM CGP 20712A) demonstrated the inability of the β2-selective antagonist ICI 118-551 to inhibit the residual lipolysis at concentrations of ICI 118-551 ≤ 1 μM. Higher concentrations of ICI 118-551 inhibited the residual formoterol-induced lipolysis competetively, but with low affinity (∼500-fold lower than its β2-adrenergic receptor pA 2, 7.80 ± 0.21), suggesting that formoterol was not acting via β2-adrenergic receptors. These data are consistent with β1-adrenergic receptors playing an important role in lipolysis at physiological but not pharmacological concentrations of catecholamines and that β2-adrenergic receptors play no obvious direct role in mediating β-adrenergic receptor agonist-induced lipolysis in vitro. Finally, racemic-SR 59230A, unlike the pure (S, S)-isomer (a β3-selective antagonist), was found to be a non-selective antagonist at the three β-adrenergic receptor subtypes, showing that the other enantiomers have different selectivity. Kluwer Academic Publishers, 2000 agonist nationallicence selective beta-adrenergic receptor blockade nationallicence white adipocytes nationallicence lipolysis nationallicence antagonist selectivity nationallicence Louis Simon Clinical Pharmacology and Therapeutics Unit, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria, Australia aut Jackman Graham Clinical Pharmacology and Therapeutics Unit, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria, Australia aut Nero Tracy Clinical Pharmacology and Therapeutics Unit, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria, Australia aut Iakovidis Dimitri Clinical Pharmacology and Therapeutics Unit, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria, Australia aut Louis William Clinical Pharmacology and Therapeutics Unit, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria, Australia aut Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/6(2000-12-01), 565-577 0920-3206 14:6<565 2000 14 10557 https://doi.org/10.1023/A:1007838125152 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1007838125152 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Louis Simon Clinical Pharmacology and Therapeutics Unit, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria, Australia aut NATIONALLICENCE 700 1- Jackman Graham Clinical Pharmacology and Therapeutics Unit, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria, Australia aut NATIONALLICENCE 700 1- Nero Tracy Clinical Pharmacology and Therapeutics Unit, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria, Australia aut NATIONALLICENCE 700 1- Iakovidis Dimitri Clinical Pharmacology and Therapeutics Unit, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria, Australia aut NATIONALLICENCE 700 1- Louis William Clinical Pharmacology and Therapeutics Unit, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria, Australia aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/6(2000-12-01), 565-577 0920-3206 14:6<565 2000 14 10557 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer