TY - JOUR
T1 - Lysophosphatidic acid (LPA) receptors are activated differentially by biological fluids
T2 - Possible role of LPA-binding proteins in activation of LPA receptors
AU - Hama, Kotaro
AU - Bandoh, Koji
AU - Kakehi, Yoshiyuki
AU - Aoki, Junken
AU - Arai, Hiroyuki
N1 - Funding Information:
We thank Drs. Takashi Izumi (Gunma University) and Takao Shimizu (University of Tokyo) for help in measurement of [Ca 2+ ] i . This work was supported in part by research grants from the Ministry of Education, Culture, Sports, Science and Technology, and by the Human Frontier Special Program.
PY - 2002/7/17
Y1 - 2002/7/17
N2 - 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.
AB - 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.
KW - Albumin
KW - EDG7
KW - LPA3
KW - Lysophosphatidic acid
KW - Nagase analbuminemic rat
KW - Seminal fluid
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U2 - 10.1016/S0014-5793(02)02976-9
DO - 10.1016/S0014-5793(02)02976-9
M3 - Article
C2 - 12123830
AN - SCOPUS:0037125239
VL - 523
SP - 187
EP - 192
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 1-3
ER -