Deorphanization of Dresden G protein-coupled receptor for an odorant receptor

J Recept Signal Transduct Res. 2007;27(4):323-34. doi: 10.1080/10799890701534180.

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.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Cyclic AMP / metabolism
  • Humans
  • Male
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / physiology*
  • Olfactory Receptor Neurons / metabolism
  • Pentanoic Acids / chemistry
  • Prostatic Neoplasms / metabolism
  • Protein Structure, Tertiary
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / physiology*
  • Receptors, Odorant / chemistry
  • Rhodopsin / chemistry

Substances

  • Neoplasm Proteins
  • OR51E1 protein, human
  • Pentanoic Acids
  • Receptors, G-Protein-Coupled
  • Receptors, Odorant
  • 3-methylvaleric acid
  • Rhodopsin
  • Cyclic AMP