Deorphanization of Dresden G Protein-Coupled Receptor for an Odorant Receptor |
| |
| Authors: | YOSHIFUMI FUJITA TOMOKO TAKAHASHI AKIKO SUZUKI KAYO KAWASHIMA FUTOSHI NARA RYUTA KOISHI |
| |
| Institution: | 1. Exploratory Research Laboratories I, Daiichi Sankyo Co., Ltd., Tokyo, Japan;2. Exploratory Research Laboratories II, Daiichi Sankyo Co., Ltd., Tokyo, Japan |
| |
| Abstract: | Dresden G protein-coupled receptor (D-GPCR) is one of orphan G protein-coupled receptors (GPCR). Here we report the identification of the ligands and the characterization of D-GPCR. We investigated over 5000 compounds to evoke the response mediated by D-GPCR and identified 3-methyl-valeric acid and 4-methyl-valeric acid as agonists using a cAMP assay. It is of interest that they dramatically enhanced the intracellular cAMP accumulation and the CRE-luciferase activity in CHO-K1 cells and HEK293 cells expressing the chimeric protein of D-GPCR with a rhodopsin-tag at its N-terminus. Our results established new characteristics of D-GPCR as an olfactory receptor. First, agonists of D-GPCR belong to odorants. Second, D-GPCR mRNA is expressed in the olfactory bulb. In addition, D-GPCR was reported to have similar sequences and its genome locus nearby other olfactory receptors. These results suggest D-GPCR is an olfactory receptor. |
| |
| Keywords: | Dresden-GPCR 3-Methyl-valeric acid orphan GPCR prostate cancer deorphanization |
|
|
