Free fatty acid receptors and drug discovery.
Utilizing the human genome database, the recently developed G-protein-coupled receptor (GPCR) deorphanizing strategy successfully identified multiple receptors of free fatty acids (FFAs) and is proposed to play a critical role in a variety of physiologic homeostasis mechanisms. GPR40 and GPR120 are activated by medium- and long-chain FFAs, whereas GPR41 and GPR43 are activated by short-chain FFAs. GPR40, which is preferentially expressed in pancreatic beta-cells, mediates insulin secretion. On the other hand, GPR120, which is abundantly expressed in the intestine, functions as a receptor for unsaturated long-chain FFAs and promotes the secretion of glucagon-like peptide-1 (GLP-1). In this review, we summarize the identification, structure, and pharmacology of the receptors and speculate on the respective physiologic roles that FFA receptor family members may play.
Hirasawa
Akira
A
Department of Genomic Drug Discovery Science, Kyoto University Graduate School of Pharmaceutical Sciences, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan. akira_h@ pharm.kyoto-u.ac.jp
Hara
Takafumi
T
Katsuma
Susumu
S
Adachi
Tetsuya
T
Tsujimoto
Gozoh
G
D000818:Animals; D015195:Drug Design; D050556:Fatty Acid-Binding Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C473034:FFAR1 protein, human; C519853:FFAR4 protein, human; D050556:Fatty Acid-Binding Proteins; D008024:Ligands; D043562:Receptors, G-Protein-Coupled