Cardiovascular Drugs and Therapy

, Volume 14, Issue 6, pp 565–577

Role of β-Adrenergic Receptor Subtypes in Lipolysis

  • Simon N.S. Louis
  • Graham P. Jackman
  • Tracy L. Nero
  • Dimitri Iakovidis
  • William J. Louis
Article

DOI: 10.1023/A:1007838125152

Cite this article as:
Louis, S.N., Jackman, G.P., Nero, T.L. et al. Cardiovasc Drugs Ther (2000) 14: 565. doi:10.1023/A:1007838125152

Abstract

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 pA2, 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.

agonistselective beta-adrenergic receptor blockadewhite adipocyteslipolysisantagonist selectivity

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Simon N.S. Louis
    • 1
  • Graham P. Jackman
    • 2
  • Tracy L. Nero
    • 2
  • Dimitri Iakovidis
    • 2
  • William J. Louis
    • 2
  1. 1.Clinical Pharmacology and Therapeutics Unit, Austin and Repatriation Medical CentreUniversity of MelbourneHeidelbergAustralia
  2. 2.Clinical Pharmacology and Therapeutics Unit, Austin and Repatriation Medical CentreUniversity of MelbourneHeidelbergAustralia