Lysophosphatidic acid (LPA) receptors are activated differentially by biological fluids: possible role of LPA‐binding proteins in activation of LPA receptors

FEBS Letters

Bandoh, Koji²  Hama, Kotaro²  Arai, Hiroyuki²  Kakehi, Yoshiyuki¹  Aoki, Junken² 

[1] Department of Urology, Kagawa Medical University, Miki-cho, Kita-gun, Kagawa 761-0793, Japan;Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

关键词: EDG7;    LPA3;    Lysophosphatidic acid;    Albumin;    Nagase analbuminemic rat;    Seminal fluid;    EDG;    endothelial cell differentiation gene;    LPA;    lysophosphatidic acid;    GPCR;    G protein-coupled receptor;    [Ca2+]i;    intracellular concentration of Ca2+ ion;    BSA;    bovine serum albumin;   

DOI  :  10.1016/S0014-5793(02)02976-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Lysophosphatidic acid (LPA) exerts multiple biological functions through G protein-coupled receptors (EDG2/LPA₁, EDG4/LPA₂, and EDG7/LPA₃) and is present in serum where it is associated with albumin. In this study we examined LPA activity in various biological fluids by measuring the LPA-induced increase in the intracellular concentration of calcium ion in three types of Sf9 insect cells, each expressing one of the LPA receptors. Using this system, we found that EDG2 and EDG4, but not EDG7, were activated strongly by addition of incubated plasma. By contrast, LPA detected in seminal plasma, which contains a low concentration of albumin, selectively activated EDG7. After LPA in these samples was extracted and reconstituted, it activated all three receptors. We also found that serum albumin readily inhibits the activation of EDG7 but not the activation of EDG2 or EDG4. In addition, plasma from Nagase analbuminemic rats but not plasma from control Sprague–Dawley rats was found to strongly activate EDG7, although the plasma of these two types of rats contained equal amounts of LPA and activated both EDG2 and EDG4. The present study shows that serum albumin can negatively regulate EDG7 but not EDG2 or EDG4, and suggests that protein factors are present in seminal plasma and deliver LPA efficiently to EDG7 but not to EDG2 or EDG4.

【 授权许可】

Unknown