Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents
| Autor: | Christine Reynet, Graeme Griffin, Lisa Sarah Gardner, Mads Tang-Christensen, Peter S. Widdowson, Helen C. Jackson, Adam J. Babbs, Hilary A. Overton, Martin James Procter, Matthew C. T. Fyfe, Geoffery M. Williams, Chrystelle Marie Rasamison, Sheila M. Doel |
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| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Physiology Molecular Sequence Data HUMDISEASE Oleic Acids White adipose tissue Pharmacology Biology Receptors G-Protein-Coupled Substrate Specificity Rats Sprague-Dawley Oleoylethanolamide chemistry.chemical_compound Mice Internal medicine Yeasts Appetite Depressants medicine Cyclic AMP Animals Humans Obesity RNA Messenger Rats Wistar Receptor Molecular Biology G protein-coupled receptor Orphan receptor Dose-Response Relationship Drug Lipid signaling Cell Biology Feeding Behavior Endocannabinoid system Diet Rats Endocrinology GPR119 chemistry SIGNALING Endocannabinoids |
| Zdroj: | Cell metabolism. 3(3) |
| ISSN: | 1550-4131 |
| Popis: | SummaryThe endogenous lipid signaling agent oleoylethanolamide (OEA) has recently been described as a peripherally acting agent that reduces food intake and body weight gain in rat feeding models. This paper presents evidence that OEA is an endogenous ligand of the orphan receptor GPR119, a G protein-coupled receptor (GPCR) expressed predominantly in the human and rodent pancreas and gastrointestinal tract and also in rodent brain, suggesting that the reported effects of OEA on food intake may be mediated, at least in part, via the GPR119 receptor. Furthermore, we have used the recombinant receptor to discover novel selective small-molecule GPR119 agonists, typified by PSN632408, which suppress food intake in rats and reduce body weight gain and white adipose tissue deposition upon subchronic oral administration to high-fat-fed rats. GPR119 therefore represents a novel and attractive potential target for the therapy of obesity and related metabolic disorders. |
| Databáze: | OpenAIRE |
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