IUPHAR/BPS Guide to Pharmacology CITE
https://doi.org/10.2218/gtopdb/F36/2020.5

Lysophospholipid (LPA) receptors (version 2020.5) in the IUPHAR/BPS Guide to Pharmacology Database



Victoria Blaho1, Jerold Chun1, Danielle Jones1, Deepa Jonnalagadda1, Yasuyuki Kihara1, Wouter Moolenaar2, Tony Ngo1, Manisha Ray1 and Valerie Tan1
  1. Sanford Burnham Prebys Medical Discovery Institute, USA
  2. Netherlands Cancer Institute, The Netherlands


Abstract

Lysophosphatidic acid (LPA) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Lysophospholipid Receptors [54, 18, 80, 125]) are activated by the endogenous phospholipid LPA. The first receptor, LPA1, was identified as ventricular zone gene-1 (vzg-1) [39], 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) [81, 102]. Binding affinities were 77-fold lower than than values obtained using radioactivity [124]. 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 [47]. LPA LPA has been proposed to be a ligand for GPCR35 [92], supported by a recent study revealing that LPA modulates macrophage function through GPR35 [53]. However CXCL17 is reported to be a ligand for GPR35/CXCR8 [74]. Moreover, LPA has also been described as an agonist for the transient receptor potential (Trp) ion channel TRPV1 [85] and TRPA1 [57]. 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.

GtoPdb is an expert-driven guide to pharmacological targets and the substances that act on them. GtoPdb is a reference work which is most usefully represented as an on-line database. As in any publication this work should be appropriately cited, and the papers it cites should also be recognized. This document provides a citation for the relevant parts of the database, and also provides a reference list for the research cited by those parts.

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

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