Identification of farnesyl pyrophosphate and N-arachidonylglycine as endogenous ligands for GPR92

Da Young Oh, Min Yoon Jung, Jin Moon Mi, Hwang Jong-Ik, Choe Han, Yeon Lee Ju, Il Kim Jae, Kim Sunoh, Rhim Hyewhon, K. O.Dell David, J. Walker Michael, Sik Na Heung, Goo Lee Min, Bang Kwon Hyuk, Kim Kyungjin, Young Seong Jae

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

A series of small compounds acting at the orphan G protein-coupled receptor GPR92 were screened using a signaling pathway-specific reporter assay system. Lipid-derived molecules including farnesyl pyrophosphate (FPP), N-arachidonylglycine (NAG), and lysophosphatidic acid were found to activate GPR92. FPP and lysophosphatidic acid were able to activate both G q/11- and Gs-mediated signaling pathways, whereas NAG activated only the Gq/11-mediated signaling pathway. Computer-simulated modeling combined with site-directed mutagenesis of GPR92 indicated that Thr97, Gly98, Phe101, and Arg267 of GPR92 are responsible for the interaction of GPR92 with FPP and NAG. Reverse transcription-PCR analysis revealed that GPR92 mRNA is highly expressed in the dorsal root ganglia (DRG) but faint in other brain regions. Peripheral tissues including, spleen, stomach, small intestine, and kidney also expressed GPR92 mRNA. Immunohistochemical analysis revealed that GPR92 is largely co-localized with TRPV1, a nonspecific cation channel that responds to noxious heat, in mouse and human DRG. FPP and NAG increased intracellular Ca2+ levels in cultured DRG neurons. These results suggest that FPP and NAG play a role in the sensory nervous system through activation of GPR92.

Original languageEnglish (US)
Pages (from-to)21054-21064
Number of pages11
JournalJournal of Biological Chemistry
Volume283
Issue number30
DOIs
StatePublished - Jul 25 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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