Oh, Da Young Yoon, Jung Min Moon, Mi Jin Hwang, Jong-Ik Choe, Han Lee, Ju Yeon Kim, Jae Il Kim, Sunoh Rhim, Hyewhon O'Dell, David K. Walker, J. Michael Na, Heung Sik Lee, Min Goo Kwon, Hyuk Bang Kim, Kyungjin Seong, Jae Young 2024-01-20T23:02:03Z 2024-01-20T23:02:03Z 2021-09-03 2008-07-25 0021-9258 https://pubs.kist.re.kr/handle/201004/133311 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 G(s)-mediated signaling pathways, whereas NAG activated only the G(q/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. English AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PROTEIN-COUPLED RECEPTOR LYSOPHOSPHATIDIC ACID CANNABINOID RECEPTOR BRAIN PAIN MEMBRANE CLONING PLASMA BINDS GPR18 Identification of farnesyl pyrophosphate and N-arachidonylglycine as endogenous ligands for GPR92 Article 10.1074/jbc.M708908200 1 JOURNAL OF BIOLOGICAL CHEMISTRY, v.283, no.30, pp.21054 - 21064 JOURNAL OF BIOLOGICAL CHEMISTRY 283 30 21054 21064 scie scopus 000257746100047 2-s2.0-51049093412 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article PROTEIN-COUPLED RECEPTOR LYSOPHOSPHATIDIC ACID CANNABINOID RECEPTOR BRAIN PAIN MEMBRANE CLONING PLASMA BINDS GPR18