Tanaka Toshiki, Yano Takeaki, Adachi Tetsuya, Koshimizu Taka-aki, Hirasawa Akira, Tsujimoto Gozoh
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 2008 Jun;377(4-6):515-22. doi: 10.1007/s00210-007-0250-y. Epub 2008 Mar 5.
We have recently found that GPR120, which is abundantly expressed in intestine, functions as a receptor for unsaturated long-chain free fatty acids (FFAs) and that GPR120 stimulation promotes the secretion of glucagons-like peptide-1 (GLP-1) in the mouse (Hirasawa et al., Nat Med 11:90-94, 2005). In this study, we cloned and characterized rat GPR120 (rGPR120), and then we examined the in vivo effects of acute and long-term administration of the natural ligand alpha-linolenic acid (alpha-LA). The cloned rat GPR120 complimentary DNA had a seven transmembrane structure, and a homology comparison of human, mouse, and rat GPR120 revealed that the rat GPR120 (rGPR120) shares 85 and 98% sequence identity with the human and mouse GPR120 proteins, respectively. The tissue distribution and ligand properties of rGPR120 were similar to those of mouse GPR120. In addition, alpha-LA provoked a transient increase in [Ca2+]i levels in HEK293 cells expressing rGPR120. Furthermore, administration of alpha-LA to the rat increased plasma GLP-1 levels, and long-term administration of alpha-LA led to proliferation of pancreatic beta cells, probably because of the enhanced GLP-1 secretion. These results show that rat GPR120 is a G-protein-coupled receptor whose ligand is a free fatty acid, and it may play an important role in the FFA-associated physiological responses.
我们最近发现，在肠道中大量表达的GPR120作为不饱和长链游离脂肪酸（FFA）的受体发挥作用，并且在小鼠中，GPR120的激活可促进胰高血糖素样肽-1（GLP-1）的分泌（平泽等人，《自然医学》11:90 - 94，2005年）。在本研究中，我们克隆并鉴定了大鼠GPR120（rGPR120），然后研究了天然配体α-亚麻酸（α-LA）急性和长期给药的体内效应。克隆的大鼠GPR120互补DNA具有七跨膜结构，对人、小鼠和大鼠GPR120的同源性比较显示，大鼠GPR120（rGPR120）与人及小鼠GPR120蛋白的序列同一性分别为85%和98%。rGPR120的组织分布和配体特性与小鼠GPR120相似。此外，α-LA可引起表达rGPR120的HEK293细胞中[Ca2+]i水平的短暂升高。此外，给大鼠注射α-LA可提高血浆GLP-1水平，长期注射α-LA可导致胰腺β细胞增殖，这可能是由于GLP-1分泌增强所致。这些结果表明，大鼠GPR120是一种G蛋白偶联受体，其配体为游离脂肪酸，它可能在与FFA相关的生理反应中发挥重要作用。
