IUPHAR/BPS Guide to Pharmacology CITE
https://doi.org/10.2218/gtopdb/F36/2019.4

Lysophospholipid (LPA) receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database



Victoria Blaho1, Jerold Chun1, Aaron Frantz1, Timothy Hla2, Danielle Jones3, Deepa Jonnalagadda1, Yasuyuki Kihara1, Hirotaka Mizuno1, Wouter Moolenaar4, Chido Mpamhanga5, Sarah Spiegel6, Valerie Tan1 and Yun C. Yung1
  1. Sanford Burnham Prebys Medical Discovery Institute, USA
  2. Cornell University, USA
  3. Scripps Research Institute, USA
  4. Netherlands Cancer Institute, The Netherlands
  5. LifeArc, UK
  6. Virginia Commonwealth University, USA


Abstract

Lysophosphatidic acid (LPA) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Lysophospholipid Receptors [50, 18]) are activated by the endogenous phospholipid LPA. The first receptor, LPA1, was identified as ventricular zone gene-1 (vzg-1) [38], leading to deorphanisation of members of the endothelial differentiation gene (edg) family as other LPA receptors along with sphingosine 1-phosphate (S1P) receptors. Additional LPA receptor GPCRs were later identified. Gene names have been codified as LPAR1, etc. to reflect the receptor function of proteins. The crystal structure of LPA1 was solved and demonstrates extracellular LPA access to the binding pocket, consistent with proposed delivery via autotaxin [12]. These studies have also implicated cross-talk with endocannabinoids via phosphorylated intermediates that can also activate these receptors. The identified receptors can account for most, although not all, LPA-induced phenomena in the literature, indicating that a majority of LPA-dependent phenomena are receptor-mediated. Binding affinities of unlabeled, natural LPA and AEAp to LPA1 were measured using backscattering interferometry (pKd = 9) [73]. Binding affinities were 77-fold lower than than values obtained using radioactivity [111]. Targeted deletion of LPA receptors has clarified signalling pathways and identified physiological and pathophysiological roles. Independent validation by multiple groups has been reported in the peer-reviewed literature for all six LPA receptors described in the tables, including further validation using a distinct read-out via a novel TGFα "shedding" assay [45]. LPA has also been described as an agonist for the transient receptor potential (Trp) ion channel TRPV1 [76] and TRPA1 [53]. LPA was originally proposed to be a ligand for GPCR35, but data show that in fact it is a receptor for CXCL17 [68]. All of these proposed non-GPCR receptor identities require confirmation and are not currently recognized as bona fide LPA receptors.

Contents

This is a citation summary for Lysophospholipid (LPA) receptors in the Guide to Pharmacology database (GtoPdb). It exists purely as an adjunct to the database to facilitate the recognition of citations to and from the database by citation analyzers. Readers will almost certainly want to visit the relevant sections of the database which are given here under database links.

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Please note that the database version for the citations given in GtoPdb are to the most recent preceding version in which the family or its subfamilies and targets were substantially changed. The links below are to the current version. If you need to consult the cited version, rather than the most recent version, please contact the GtoPdb curators.

Database links

Lysophospholipid (LPA) receptors
http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=36
Introduction to Lysophospholipid (LPA) receptors
http://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=36
    Receptors
            LPA1 receptor
            http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=272
            LPA2 receptor
            http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=273
            LPA3 receptor
            http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=274
            LPA4 receptor
            http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=94
            LPA5 receptor
            http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=124
            LPA6 receptor
            http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=163

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