Lysophosphatidic acid is a mediator of Trp-Lys-Tyr-Met-Val-d-Met-induced calcium influx.
Intracellular calcium (Ca(2+)) homeostasis is very strictly regulated, and the activation of G-protein-coupled receptor (GPCR) can cause two different calcium changes, intracellular calcium release, and calcium influx. In this study, we investigated the possible role of lysophosphatidic acid (LPA) on GPCR-induced Ca(2+) signaling. The addition of exogenous LPA induced dramatic Ca(2+) influx but not intracellular Ca(2+) release in U937 cells. LPA-induced Ca(2+) influx was not affected by pertussis toxin and phospholipase C inhibitor (U73122), ruling out the involvement of pertussis toxin-sensitive G-proteins, and phospholipase C. Stimulation of U937 cells with Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), which binds to formyl peptide receptor like 1, enhanced phospholipase A(2) and phospholipase D activation, indicating LPA formation. The inhibition of LPA synthesis by phospholipase A(2)-specific inhibitor (MAFP) or n-butanol significantly inhibited WKYMVm-induced Ca(2+) influx, suggesting a crucial role for LPA in the process. Taken together, we suggest that LPA mediates WKYMVm-induced Ca(2+) influx.
Lee
Ha-Young
HY
Medical Research Center for Cancer Molecular Therapy, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.
Kang
Hyun-Kyu
HK
Yoon
Hye-Ran
HR
Kwak
Jong-Young
JY
Bae
Yoe-Sik
YS
D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D044042:Receptors, Formyl Peptide / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D044067:Receptors, Lipoxin / Q000378:metabolism
C105101:FPR2 protein, human; D008246:Lysophospholipids; D009842:Oligopeptides; D044042:Receptors, Formyl Peptide; D043562:Receptors, G-Protein-Coupled; D044067:Receptors, Lipoxin; C113617:Trp-Lys-Tyr-Met-Val-Met; D016718:Arachidonic Acid; D010741:Phospholipases A; D010739:Phospholipase D; C032881:lysophosphatidic acid; D002118:Calcium