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Title: Role of beta-adrenergic receptor subtypes in lipolysis.
Austin Authors: Louis, Simon N S;Jackman, G P;Nero, Tracy L;Iakovidis, D;Louis, William J 
Affiliation: University of Melbourne, Clinical Pharmacology and Therapeutics Unit, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia
Issue Date: 1-Dec-2000
Publication information: Cardiovascular Drugs and Therapy / Sponsored By the International Society of Cardiovascular Pharmacotherapy; 14(6): 565-77
Abstract: In vitro lipolysis stimulated by low (-)-isoprenaline concentrations (< or =30 nM) in epididymal white adipocytes from Sprague-Dawley rats was inhibited at least 60-80% by the specific beta1-antagonists LK 204-545 and CGP 20712A (1 microM), suggesting that at these low (10 nM) concentrations of (-)-isoprenaline lipolysis was primarily (80%) but not solely mediated via beta1-adrenergic receptors. Low concentrations (100 nM) of (-)-noradrenaline and formoterol also confirmed a role for beta1-adrenergic receptors in mediating lipolysis at low concentrations of these agonists. At higher agonist concentrations, beta3-adrenergic receptors were fully activated and were the dominant beta-adrenergic receptor subtype mediating the maximum lipolytic response, and the maximum response was not affected by the beta1-antagonists, demonstrating that the beta3-receptor is capable of inducing maximum lipolysis on its own. Studies of lipolysis induced by the relatively beta2-selective agonist formoterol in the presence of beta1-blockade (1 microM CGP 20712A) demonstrated the inability of the beta2-selective antagonist ICI 118-551 to inhibit the residual lipolysis at concentrations of ICI 118-551 < or = 1 microM. Higher concentrations of ICI 118-551 inhibited the residual formoterol-induced lipolysis competetively, but with low affinity (approximately 500-fold lower than its beta2-adrenergic receptor pA2, 7.80 +/- 0.21), suggesting that formoterol was not acting via beta2-adrenergic receptors. These data are consistent with beta1-adrenergic receptors playing an important role in lipolysis at physiological but not pharmacological concentrations of catecholamines and that beta2-adrenergic receptors play no obvious direct role in mediating beta-adrenergic receptor agonist-induced lipolysis in vitro. Finally, racemic-SR 59230A, unlike the pure (S, S)-isomer (a beta3-selective antagonist), was found to be a nonselective antagonist at the three beta-adrenergic receptor subtypes, showing that the other enantiomers have different selectivity.
Gov't Doc #: 11300357
Type: Journal Article
Subjects: Adipocytes.drug effects.metabolism
Adrenergic beta-Agonists.pharmacology
Adrenergic beta-Antagonists.pharmacology
Dose-Response Relationship, Drug
Heart Rate.drug effects
In Vitro Techniques
Rats, Sprague-Dawley
Receptors, Adrenergic, beta.physiology
Receptors, Adrenergic, beta-1.physiology
Receptors, Adrenergic, beta-2.physiology
Receptors, Adrenergic, beta-3.physiology
Appears in Collections:Journal articles

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