Structure-activity relationships of fatty acid amide ligands in activating and desensitizing G protein-coupled receptor 119
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- 作者：Pritesh Kumar ; Akhilesh Kumar ; Zhao-Hui Song
- 关键词：G protein-coupled receptor 119 ; Fatty acid amides ; Structure-activity relationship
- 刊名：European Journal of Pharmacology
- 出版年：15 January, 2014
- 年：2014
- 卷：723
- 期：Complete
- 页码：465-472
- 全文大小：674 K
文摘
The purpose of the current study was to apply a high throughput assay to investigate the structure-activity relationships of fatty acid amides for activating and desensitizing G protein-coupled receptor 119, a promising therapeutic target for both type 2 diabetes and obesity. A cell-based, homogenous time resolved fluorescence (HTRF) method for measuring G protein-coupled receptor 119-mediated increase of cyclic adenosine monophosphate (cAMP) levels was validated and applied in this study. Using novel fatty acid amides and detailed potency and efficacy analyses, we have demonstrated that degree of saturation in acyl chain and charged head groups of fatty acid amides have profound effects on the ability of these compounds to activate G protein-coupled receptor 119. In addition, we have demonstrated for the first time that pretreatments with G protein-coupled receptor 119 agonists desensitize the receptor and the degrees of desensitization caused by fatty acid amides correlate well with their structure-activity relationships in activating the receptor.