Assessment of agonism at G‐protein coupled receptors by phosphatidic acid and lysophosphatidic acid in human embryonic kidney 293 cells

Abstract
Several different molecular species of phosphatidic acid (PA) bind to a G‐protein coupled receptor (GPCR) to induce activation of the p42/p44 mitogen‐activated protein kinase (p42/p44 MAPK) pathway in HEK 293 cells. PA is active at low nanomolar concentrations and the response is sensitive to pertussis toxin (which uncouples GPCRs from Gi/o). The de‐acylated product of PA, lysophosphatidic acid (LPA), which binds to members of the endothelial differentiation gene (EDG) family of receptors also stimulated p42/p44 MAPK in a pertussis toxin sensitive manner, but with an ∼100 – 1000 fold lower potency compared with the different molecular species of PA. RT – PCR using gene‐specific primers showed that HEK 293 cells express EDG2 and PSP24, the latter being a lipid binding GPCR out with the EDG cluster. We conclude that PA is a novel high potency GPCR agonist.British Journal of Pharmacology (2001) 134, 6–9; doi:10.1038/sj.bjp.0704278

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