Document Detail


Novel selective ligands for free fatty acid receptors GPR120 and GPR40.
MedLine Citation:
PMID:  19471906     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
GPR120 and GPR40 are G-protein-coupled receptors whose endogenous ligands are medium- and long-chain free fatty acids, and they are thought to play an important physiological role in insulin release. Despite recent progress in understanding their roles, much still remains unclear about their pharmacology, and few specific ligands for GPR120 and GPR40 besides medium- to long-chain fatty acids have been reported so far. To identify new selective ligands for these receptors, more than 80 natural compounds were screened, together with a reference compound MEDICA16, which is known to activate GPR40, by monitoring the extracellular regulated kinase (ERK) and [Ca(2+)](i) responses in inducible and stable expression cell lines for GPR40 and GPR120, respectively. MEDICA16 selectively activated [Ca(2+)](i) response in GPR40-expressing cells but not in GPR120-expressing cells. Among the natural compounds tested, grifolin derivatives, grifolic acid and grifolic acid methyl ether, promoted ERK and [Ca(2+)](i) responses in GPR120-expressing cells, but not in GPR40-expressing cells, and inhibited the alpha-linolenic acid (LA)-induced ERK and [Ca(2+)](i) responses in GPR120-expressing cells. Interestingly, in accordance with the pharmacological profiles of these compounds, similar profiles of glucagon-like peptide-1 secretion were seen for mouse enteroendocrine cell line, STC-1 cells, which express GPR120 endogenously. Taken together, these studies identified a selective GPR40 agonist and several GPR120 partial agonists. These compounds would be useful probes to further investigate the physiological and pharmacological functions of GPR40 and GPR120.
Authors:
Takafumi Hara; Akira Hirasawa; Qi Sun; Keiko Sadakane; Chisato Itsubo; Tomoyo Iga; Tetsuya Adachi; Taka-aki Koshimizu; Toshihiro Hashimoto; Yoshinori Asakawa; Gozoh Tsujimoto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-27
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  380     ISSN:  1432-1912     ISO Abbreviation:  Naunyn Schmiedebergs Arch. Pharmacol.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-07-23     Completed Date:  2009-09-22     Revised Date:  2011-11-03    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  247-55     Citation Subset:  IM    
Affiliation:
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimo-adachi-cho, Sakyo-ku, Kyoto, Japan. t-hara@fc.ritsumei.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium / metabolism
Cell Line
Extracellular Signal-Regulated MAP Kinases / drug effects,  metabolism
Humans
Ligands
Mice
Palmitic Acids / pharmacology
Receptors, G-Protein-Coupled / agonists*
Terpenes / chemistry,  pharmacology
Chemical
Reg. No./Substance:
0/FFAR1 protein, human; 0/Ligands; 0/O3FAR1 protein, human; 0/Palmitic Acids; 0/Receptors, G-Protein-Coupled; 0/Terpenes; 6379-55-1/grifolin; 7440-70-2/Calcium; 87272-20-6/MEDICA 16; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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