Free fatty acid receptors and drug discovery
Free fatty acid receptors and drug discovery
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DOI：
10.1248/bpb.31.1847
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发表时间：
2008-10-01
影响因子：
2
通讯作者：
Tsujimoto, Gozoh
中科院分区：
文献类型：
--
作者：
Hirasawa, Akira;Hara, Takafumi;Tsujimoto, Gozoh
利用人类基因组数据库，最近开发的G-蛋白偶联受体（GPCR）去乙酰化策略成功地确定了多种游离脂肪酸（FFA）受体，并提出在各种生理稳态机制中发挥关键作用。GPR 40和GPR 120由中链和长链FFA激活，而GPR 41和GPR 43由短链FFA激活。GPR 40优先在胰腺β细胞中表达，介导胰岛素分泌。另一方面，在肠中大量表达的CPR 120作为不饱和长链FFA的受体发挥功能，促进胰高血糖素样肽-1（GLP-1）的分泌。在这篇综述中，我们总结了识别，结构和受体的药理学和推测FFA受体家族成员可能发挥各自的生理作用。
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, CPR120, 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.