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Lysophosphatidic acid (LPA) enhances barrier function in intralobar rat pulmonary artery endothelial cells
Author(s) -
Umesh Anita,
Cornfield David N.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.797.12
Subject(s) - lysophosphatidic acid , pertussis toxin , autotaxin , barrier function , chemistry , extracellular , sphingosine , microbiology and biotechnology , sphingosine 1 phosphate , endocrinology , medicine , receptor , biology , g protein , biochemistry
Lysophosphatidic acid (LPA) is a bioactive serum lipid whose levels are increased in atherosclerotic plaques. In endothelial cells (ECs), LPA promotes migration, adhesion, wound healing, and modulates barrier function, in part, via 6 receptors (LPA1–6). While its sphingolipid homologue sphingosine‐1‐phosphate, enhances PAEC barrier function, the LPA effects on PAECs are unknown. Here we hypothesized that LPA also enhances PAEC barrier function. To test this, we determined the expression of LPA1–6, GPR87 and P2Y10; and examined the LPA effects on PAEC transendothelial resistance (TER), cytosolic calcium ([Ca 2+ ] i ), and [cAMP] in ECs isolated from 3 rd /4 th generation intralobar rat PAs. Intralobar PAECs express non‐Edg LPA4/p2y9/GPR23 and LPA6/p2y5. Low [LPA] (0.1uM) increased TER by 4.9±0.6 % (t=30m), while 10uM LPA initially decreased TER by 10.4±1.0% (t=10m) followed by a sustained rise of 14.4 ± 2.1 % (t=90m). LPA increased [Ca 2+ ] i dose‐dependently, and [cAMP] in the presence of forskolin that was potentiated by pertussis toxin (PTX). Both entry and release mechanisms contribute to the LPA‐induced Ca transients since absence of extracellular Ca reduced the signal by 70±10% (p<0.05). LPA‐induced Ca entry was PTX‐sensitive, while release was PTX‐insensitive. Based on these data, we conclude that circulating [LPA] enhance PAEC barrier function and modulates [Ca 2+ ] i and [cAMP] via LPA4 activation.