Lysophosphatidic acid binds to and activates GPR92, a G protein-coupled receptor highly expressed in gastrointestinal lymphocytes

被引:182
作者
Kotarsky, Knut
Boketoft, Ake
Bristulf, Jesper
Nilsson, Niclas E.
Norberg, Ake
Hansson, Stefan
Owman, Christer
Sillard, Rannar
Leeb-Lundberg, L. M. Fredrik
Olde, Bjoern
机构
[1] Lund Univ, Div Immunol, Lund, Sweden
[2] Lund Univ, Div Cellular & Mol Pharmacol, Dept Expt Med Sci, Lund, Sweden
[3] Lund Univ, Div Obstet & Gynecol, Dept Clin Sci, Lund, Sweden
[4] HeptaHelix AB, Malmo, Sweden
[5] Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden
关键词
D O I
10.1124/jpet.105.098848
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Here, the ligand binding, activation, and tissue distribution of the orphan G protein-coupled receptor (GPCR) GPR92 were studied. GPR92 binds and is activated by compounds based on the lysophosphatidic acid (LPA) backbone. The binding of LPA to GPR92 was of high affinity (K-D = 6.4 +/- 0.9 nM) and led to an increase in both phosphoinositide hydrolysis and cAMP production. GPR92 is atypical in that it has a low sequence homology with the classic LPA(1-3) receptors (21-22%). Expression of GPR92 is mainly found in heart, placenta, spleen, brain, lung, and gut. Notably, GPR92 is highly expressed in the lymphocyte compartment of the gastrointestinal tract. It is the most abundant GPCR activated by LPA found in the small intestinal intraepithelial CD8(+) cytotoxic T cells.
引用
收藏
页码:619 / 628
页数:10
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