Deorphanization of Dresden G protein-coupled receptor for an odorant receptor.
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.
Fujita
Yoshifumi
Y
Exploratory Research Laboratories I, Daiichi Sankyo Co., Ltd., Tokyo, Japan. fujita.yoshifumi.z6@daiichisankyo.co.jp
Takahashi
Tomoko
T
Suzuki
Akiko
A
Kawashima
Kayo
K
Nara
Futoshi
F
Koishi
Ryuta
R
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000737:chemistry / Q000502:physiology*; D018034:Olfactory Receptor Neurons / Q000378:metabolism; D010421:Pentanoic Acids / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000502:physiology*; D018035:Receptors, Odorant / Q000737:chemistry; D012243:Rhodopsin / Q000737:chemistry
D009363:Neoplasm Proteins; C510734:OR51E1 protein, human; D010421:Pentanoic Acids; D043562:Receptors, G-Protein-Coupled; D018035:Receptors, Odorant; C042993:3-methylvaleric acid; D012243:Rhodopsin; D000242:Cyclic AMP