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Received for publication May 16, 2005.
Revised June 6, 2005.
Accepted for publication June 6, 2005.
1/
2/
3 -adrenoceptor Knockout Mice
Catecholamines are major stimulants of adipose tissue metabolism. Norepinephrine and epinephrine act through three subtypes of
-adrenoceptors (
-AR) expressed in the adipocytes. The aim of this work was to study the mechanisms of lipid mobilization in
1/
2/
3-AR triple knockout (
-less) mice. Glycerol and non-esterified 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 adrenocorticotropic hormone or to agents acting at the adenylyl cyclase and protein kinase A levels. The lipolytic response to norepinephrine and
-AR agonists was blunted in
-less mice. However, a residual low affinity lipolytic effect was observed in the presence of catecholamines and
3-AR agonists but not of
1- or
2-AR agonists. cAMP levels were increased by a
-AR agonist in white and brown adipocytes of
-less mice. The residual lipolytic effect was blocked by
-AR antagonists. It was mediated neither by
1- or
2-AR nor by dopaminergic, serotoninergic and histaminergic receptors. Bioinformatic analyses do not provide evidence for a fourth
-AR. We conclude that the residual lipolytic effect observed in
-less mice can be attributed to an unknown Gs-protein-coupled receptor with low affinity for catecholamines.
Key words:
Adrenergic, Gs family, cAMP
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