Identification of GPR55 as a lysophosphatidylinositol receptor.
GPR55 is an orphan G protein-coupled receptor. In this study, we explored a possible endogenous ligand for GPR55 using HEK293 cells which expressed GPR55. We found that lysophosphatidylinositol induced rapid phosphorylation of the extracellular signal-regulated kinase in transiently or stably GPR55-expressing cells. On the other hand, lysophosphatidylinositol did not induce phosphorylation of the extracellular signal-regulated kinase in vector-transfected cells. Lysophosphatidic acid and sphingosine 1-phosphate also induced phosphorylation of the extracellular signal-regulated kinase in GPR55-expressing cells. However, these lipid phosphoric acids elicited similar responses in vector-transfected cells. Various types of other lysolipids as well as the cannabinoid receptor ligands did not induce phosphorylation of the extracellular signal-regulated kinase. We also found that lysophosphatidylinositol elicited a rapid Ca2+ transient in GPR55-expressing cells. Lysophosphatidylinositol also stimulated the binding of GTPgammaS to the GPR55-expressing cell membranes. These results strongly suggest that GPR55 is a specific and functional receptor for lysophosphatidylinositol.
Oka
Saori
S
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa 229-0195, Japan.
Nakajima
Keisuke
K
Yamashita
Atsushi
A
Kishimoto
Seishi
S
Sugiura
Takayuki
T
D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D011485:Protein Binding; D043882:Receptors, Cannabinoid; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D049312:Receptors, Lysophospholipid / Q000737:chemistry* / Q000378:metabolism*
C118065:G-protein-coupled receptor 34; C524885:GPR55 protein, human; D043882:Receptors, Cannabinoid; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid