Regulation of peptides secretion by orphan G protein coupled receptor
| Project/Area Number |
18390024
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
HIRASAWA Akira Kyoto University, Graduate School of Pharmaceutical Sciences, Associate Professor (70242633)
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| Co-Investigator(Kenkyū-buntansha) |
AWAJI Takeo Tokyo Women's Medical University, School of Medicine, Lecturer (60297546)
HAYANO Toshiya Ritsumeikan University, College of Information Science and Engineering, Professor (90332303)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,060,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2007: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2006: ¥10,300,000 (Direct Cost: ¥10,300,000)
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| Keywords | Proteome / signal transduction / Microarray / pharmaceutical sciences / genome / オーファン受容体 / 脂肪酸 / 分泌 / ペプチド / 脂肪酸受容体 / 質量分析 |
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| Research Abstract |
Agonist activation of a G protein-coupled receptor (GPCR) results in the redistribution of the receptor protein away from the cell surface into internal cellular compartments through a process of endocytosis known as internalization. We examined whether the ligand-mediated internalization of a GPCR can be exploited for pharmacological evaluations. We acquired fluorescent images of cells expressing GFP-labeled GPCRs and evaluated the ligand-mediated internalization quantitatively by image processing. The rank order of receptor internalization potency for a variety of agonists and antagonists specific to each receptor corresponded well with that previously observed in ligand binding studies. In addition to chemical ligand-induced internalization, this cell-based fluorescence imaging system successfully monitored the internalization of the proton-sensing GPCR TDAG8, and that of the free fatty acid-sensitive GPCR GPR120. The results show. That monitoring receptor internalization can be a u
… More
seful approach for pharmacological characterization of GPCRs and in fishing for ligands of orphan GPCRs.
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. The ingestion of fat induces secretion of the gut peptide hormone cholecystokinin (CCK). In this study, we examined whether these FFA receptors mediate-lipid-induced CCK and other peptide release in the mouse. We first observed that intra-gastric administration of long-chain FFAs increased plasma CCK levels. Using mouse enteroendocrine STC-1 cells as a model system, we further studied the mechanism of this FFA induced CCK secretion_ Long-chain FFAs promoted CCK secretion from STC-1 cells, which was abolished either by removal of extracellular Ca2+or by the L-type Ca^<2+>channel blacker nicardipine. Furthermore, this FFA-induced CCK secretion was specifically inhibited by transfection of GPR120-specific, but not GPR40-specific, short hairpin RNA. These results indicate that long-chain FFAs induce CCK secretion through GPR120-coupled Ca^<2+>signaling. Less
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Report
(3 results)
Research Products
(63 results)
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[Journal Article] The regulation of adipogenesis through GPR1202007
Author(s)
Gotoh C, Hong YH, Iga T, Hishikawa D, Suzuki Y, Song SH, Choi KC, Adachi T, Hirasawa A, Tsujimoto G, Sasaki S, Roh SG.
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Journal Title
Biochem Biophys Res Commun. 354(2)
Pages: 591-597
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[Journal Article] Developmental aberrations of liver gene expression in bovine fetuses derived from somatic cell nuclear transplantation.2006
Author(s)
Herath CB, Ishiwata H, Shiojima S, Kadowaki T, Katsuma S, Ushizawa K, Imai K, Takahashi T, Hirasawa A, Takahashi S, Izaike Y, Tsujimoto G, Hashizume K..
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Journal Title
Cloning Stem Cells. 8(2)
Pages: 79-95
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[Presentation] 脂肪酸受容体の生理機能2007
Author(s)
平澤 明
Organizer
第80回日本薬理学会年会
Place of Presentation
名古屋国際会議場
Year and Date
2007-03-14
Description
「研究成果報告書概要(和文)」より
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