Lysophospholipid (LPA) receptors

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Lysophosphatidic acid (LPA) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Lysophospholipid Receptors [1,9]) are activated by the endogenous phospholipid metabolite LPA. The first receptor, LPA1, was identified as ventricular zone gene-1 (vzg-1), 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 recently solved and demonstrates extracellular LPA access to the binding pocket, consistent with proposed delivery via autotaxin. 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. Radioligand binding has been conducted in heterologous expression systems using [3H]LPA (e.g. [4]). In native systems, analysis of binding data is complicated by metabolism and high levels of nonspecific binding, and therefore the relationship between recombinant and endogenously expressed receptors is unclear. 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 [8]. LPA has also been described as an agonist for the transient receptor potential (Trp) ion channel TRPV1 [16]. In addition, orphan GPCRs (PSP24, GPR87, and GPR35), as well as the nuclear hormone receptor PPARγ [15,19], have been reported as LPA receptors, although these identities require confirmation and are not currently recognized as bona fide LPA receptors.

Receptors

LPA1 receptor Show summary » More detailed page

LPA2 receptor Show summary » More detailed page

LPA3 receptor Show summary » More detailed page

LPA4 receptor Show summary » More detailed page

LPA5 receptor Show summary » More detailed page

LPA6 receptor Show summary » More detailed page

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References

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NC-IUPHAR subcommittee and family contributors

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How to cite this family page

Database page citation:

Jerold Chun, Timothy Hla, Wouter Moolenaar, Sarah Spiegel, Yun C. Yung, Chido Mpamhanga. Lysophospholipid (LPA) receptors. Accessed on 14/02/2016. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=36.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Davenport AP, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: G protein-coupled receptors. Br J Pharmacol. 172: 5744-5869.