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Molecular Pharmacology

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Research ArticleArticle

Norepinephrine Induces Lipolysis in β1/β2/β3-Adrenoceptor Knockout Mice

Geneviève Tavernier, Maria Jimenez, Jean-Paul Giacobino, Nicolas Hulo, Max Lafontan, Patrick Muzzin and Dominique Langin
Molecular Pharmacology September 2005, 68 (3) 793-799; DOI: https://doi.org/10.1124/mol.105.014670
Geneviève Tavernier
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Maria Jimenez
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Jean-Paul Giacobino
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Nicolas Hulo
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Max Lafontan
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Patrick Muzzin
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Dominique Langin
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Abstract

Catecholamines are major stimulants of adipose tissue metabolism. Norepinephrine and epinephrine act through three subtypes of β-adrenoceptors (β-AR) expressed in the adipocytes. The aim of this work was to study the mechanisms of lipid mobilization in β1/β2/β3-AR triple-knockout (β-less) mice. Glycerol and nonesterified fatty acids released from isolated adipocytes were measured as an index of lipolytic activity. There was no difference between the two genotypes for basal lipolysis and lipolytic response to corticotropin or to agents acting at the adenylyl cyclase and protein kinase A levels. The lipolytic response to norepinephrine and β-AR agonists was blunted in β-less mice. However, a residual low-affinity lipolytic effect was observed in the presence of catecholamines and β3-AR agonists but not of β1- or β2-AR agonists. cAMP levels were increased by a β-AR agonist in white and brown adipocytes of β-less mice. The residual lipolytic effect was blocked by β-AR antagonists. It was mediated neither by α1- or α2-AR nor dopaminergic, serotonergic, and histaminergic by receptors. Bioinformatic analyses do not provide evidence for a fourth β-AR. We conclude that the residual lipolytic effect observed in β-less mice can be attributed to an unknown Gs-protein-coupled receptor with low affinity for catecholamines.

  • Received May 11, 2005.
  • Accepted June 6, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 68 (3)
Molecular Pharmacology
Vol. 68, Issue 3
1 Sep 2005
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Research ArticleArticle

Norepinephrine Induces Lipolysis in β1/β2/β3-Adrenoceptor Knockout Mice

Geneviève Tavernier, Maria Jimenez, Jean-Paul Giacobino, Nicolas Hulo, Max Lafontan, Patrick Muzzin and Dominique Langin
Molecular Pharmacology September 1, 2005, 68 (3) 793-799; DOI: https://doi.org/10.1124/mol.105.014670

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Research ArticleArticle

Norepinephrine Induces Lipolysis in β1/β2/β3-Adrenoceptor Knockout Mice

Geneviève Tavernier, Maria Jimenez, Jean-Paul Giacobino, Nicolas Hulo, Max Lafontan, Patrick Muzzin and Dominique Langin
Molecular Pharmacology September 1, 2005, 68 (3) 793-799; DOI: https://doi.org/10.1124/mol.105.014670
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