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Journal of Biochemistry Advance Access published online on October 9, 2008
Journal of Biochemistry, doi:10.1093/jb/mvn136
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© 2008 The Japanese Biochemical Society

2-Arachidonoyl-sn-glycero-3-phosphoinositol: A Possible Natural Ligand for GPR55

Saori Oka, Toshinobu Toshida, Kanako Maruyama, Keisuke Nakajima, Atsushi Yamashita and Takayuki Sugiura*

Faculty of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa 229-0195, Japan

*To whom correspondence should be addressed. Dr. Takayuki Sugiura. Tel: +81-(0)42-685-3746, Fax: +81-(0)42-685-1345, E-mail: sugiurat{at}pharm.teikyo-u.ac.jp

Received August 15, 2008; Accepted September 26, 2008


  Abstract

GPR55 is a G protein-coupled receptor. Recently, we obtained evidence that lysophosphatidylinositol is a possible endogenous ligand for GPR55. However, no information is currently available concerning the biological activities of the individual molecular species of lysophosphatidylinositol. Furthermore, little is known concerning the levels as well as the molecular species of lysophosphatidylinositol in mammalian tissues. In this study, we first examined whether lysophosphatidylinositol is present in rat brain. We found that rat brain contains 37.5 nmol/g tissue of lysophosphatidylinositol; the most predominant fatty acyl moiety is stearic acid (50.5%) followed by arachidonic acid (22.1%). We next compared the biological activities of various molecular species of lysophosphatidylinositol and related molecules using HEK293 cells expressing GPR55. We found that the level of biological activity of the 2-arachidonoyl species is markedly higher than those of others. These results strongly suggest that the 2-arachidonoyl species of lysophosphatidylinositol is the true natural ligand for GPR55.

Key Words: 2-arachidonoyl-sn-glycero-3-phosphoinositol, cannabinoid, G protein-coupled receptor, GPR55, lysophosphatidylinositol


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