Lysophospholipid (LPA) receptors
More information on this family may be found on the IUPHAR-DB family and introduction pages.
Lysophosphatidic acid (LPA) receptors (nomenclature as agreed by NC-IUPHAR Subcommittee on Lysophospholipid Receptors; [2]) are activated by the endogenous lipid derivative LPA. Originally identified as members of the endothelial differentiation gene (edg) family along with sphingosine 1-phosphate receptors, the gene names have recently been updated to LPAR1, etc. to reflect the receptor function of these proteins. 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. LPA has also been described to be an agonist at PPARγ receptors [10], although the physiological significance of this observation remains unclear [13].
Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Receptors 
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Aoki, J; Inoue, A; Okudaira, S. (2008) Two pathways for lysophosphatidic acid production. Biochim. Biophys. Acta, 1781 (9): 513-8. [PMID:18621144]
Choi, JW; Herr, DR; Noguchi, K; Yung, YC; Lee, CW; Mutoh, T; Lin, ME; Teo, ST; Park, KE; Mosley, AN; Chun, J. (2010) LPA receptors: subtypes and biological actions. Annu. Rev. Pharmacol. Toxicol., 50: 157-86. [PMID:20055701]
Chun, J; Hla, T; Lynch, KR; Spiegel, S; Moolenaar, WH. (2010) International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid receptor nomenclature. Pharmacol. Rev., 62 (4): 579-87. [PMID:21079037]
Georas, SN. (2009) Lysophosphatidic acid and autotaxin: emerging roles in innate and adaptive immunity. Immunol. Res., [Epub ahead of print]. [PMID:19184538]
Hama, K; Aoki, J. (2010) LPA(3), a unique G protein-coupled receptor for lysophosphatidic acid. Prog. Lipid Res., 49 (4): 335-42. [PMID:20230855]
Ishii, S; Noguchi, K; Yanagida, K. (2009) Non-Edg family lysophosphatidic acid (LPA) receptors. Prostaglandins Other Lipid Mediat., 89 (3-4): 57-65. [PMID:19524700]
Lin, ME; Herr, DR; Chun, J. (2010) Lysophosphatidic acid (LPA) receptors: signaling properties and disease relevance. Prostaglandins Other Lipid Mediat., 91 (3-4): 130-8. [PMID:20331961]
Meyer zu Heringdorf, D; Jakobs, KH. (2007) Lysophospholipid receptors: signalling, pharmacology and regulation by lysophospholipid metabolism. Biochim. Biophys. Acta, 1768 (4): 923-40. [PMID:17078925]
Mutoh, T; Chun, J. (2008) Lysophospholipid activation of G protein-coupled receptors. Subcell. Biochem., 49: 269-97. [PMID:18751915]
Noguchi, K; Herr, D; Mutoh, T; Chun, J. (2009) Lysophosphatidic acid (LPA) and its receptors. Curr Opin Pharmacol, 9 (1): 15-23. [PMID:19119080]
Pyne, NJ; Pyne, S. (2008) Sphingosine 1-phosphate, lysophosphatidic acid and growth factor signaling and termination. Biochim. Biophys. Acta, 1781 (9): 467-76. [PMID:18558100]
Shimizu, T. (2009) Lipid mediators in health and disease: enzymes and receptors as therapeutic targets for the regulation of immunity and inflammation. Annu. Rev. Pharmacol. Toxicol., 49: 123-50. [PMID:18834304]
Sun, W; Yang, J. (2010) Molecular basis of lysophosphatidic acid-induced NF-κB activation. Cell. Signal., 22 (12): 1799-803. [PMID:20471472]
Swaney, JS; Chapman, C; Correa, LD; Stebbins, KJ; Bundey, RA; Prodanovich, PC; Fagan, P; Baccei, CS; Santini, AM; Hutchinson, JH; et al.. (2010) A novel, orally active LPA(1) receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. Br. J. Pharmacol., 160 (7): 1699-713. [PMID:20649573]
Tigyi, G. (2010) Aiming drug discovery at lysophosphatidic acid targets. Br. J. Pharmacol., 161 (2): 241-70. [PMID:20735414]
1. Bagga, S; Price, KS; Lin, DA; Friend, DS; Austen, KF; Boyce, JA. (2004) Lysophosphatidic acid accelerates the development of human mast cells. Blood, 104 (13): 4080-7. [PMID:15319282]
2. Chun, J; Hla, T; Lynch, KR; Spiegel, S; Moolenaar, WH. (2010) International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid receptor nomenclature. Pharmacol. Rev., 62 (4): 579-87. [PMID:21079037]
3. Fischer, DJ; Nusser, N; Virag, T; Yokoyama, K; Wang Da; Baker, DL; Bautista, D; Parrill, AL; Tigyi, G. (2001) Short-chain phosphatidates are subtype-selective antagonists of lysophosphatidic acid receptors. Mol. Pharmacol., 60 (4): 776-84. [PMID:11562440]
4. Fukushima, N; Kimura, Y; Chun, J. (1998) A single receptor encoded by vzg-1/lpA1/edg-2 couples to G proteins and mediates multiple cellular responses to lysophosphatidic acid. Proc. Natl. Acad. Sci. U.S.A., 95 (11): 6151-6. [PMID:9600933]
5. Hasegawa, Y; Erickson, JR; Goddard, GJ; Yu, S; Liu, S; Cheng, KW; Eder, A; Bandoh, K; Aoki, J; Jarosz, R; et al.. (2003) Identification of a phosphothionate analogue of lysophosphatidic acid (LPA) as a selective agonist of the LPA3 receptor. J. Biol. Chem., 278 (14): 11962-9. [PMID:12554733]
6. Kimura, T; Mogi, C; Sato, K; Tomura, H; Ohta, H; Im, DS; Kuwabara, A; Kurose, H; Murakami, M; Okajima, F. (2011) p2y5/LPA(6) attenuates LPA(1)-mediated VE-cadherin translocation and cell-cell dissociation through G(12/13) protein-Src-Rap1. Cardiovasc. Res., 92 (1): 149-58. [PMID:21632882]
7. Kotarsky, K; Boketoft, A; Bristulf, J; Nilsson, NE; Norberg, A; Hansson, S; Owman, C; Sillard, R; Leeb-Lundberg, LM; Olde, B. (2006) Lysophosphatidic acid binds to and activates GPR92, a G protein-coupled receptor highly expressed in gastrointestinal lymphocytes. J. Pharmacol. Exp. Ther., 318 (2): 619-28. [PMID:16651401]
8. Lee, CW; Rivera, R; Dubin, AE; Chun, J. (2007) LPA(4)/GPR23 is a lysophosphatidic acid (LPA) receptor utilizing G(s)-, G(q)/G(i)-mediated calcium signaling and G(12/13)-mediated Rho activation. J. Biol. Chem., 282 (7): 4310-7. [PMID:17166850]
9. Lee, CW; Rivera, R; Gardell, S; Dubin, AE; Chun, J. (2006) GPR92 as a new G12/13- and Gq-coupled lysophosphatidic acid receptor that increases cAMP, LPA5. J. Biol. Chem., 281 (33): 23589-97. [PMID:16774927]
10. McIntyre, TM; Pontsler, AV; Silva, AR; St Hilaire, A; Xu, Y; Hinshaw, JC; Zimmerman, GA; Hama, K; Aoki, J; Arai, H; et al.. (2003) Identification of an intracellular receptor for lysophosphatidic acid (LPA): LPA is a transcellular PPARgamma agonist. Proc. Natl. Acad. Sci. U.S.A., 100 (1): 131-6. [PMID:12502787]
11. Ohta, H; Sato, K; Murata, N; Damirin, A; Malchinkhuu, E; Kon, J; Kimura, T; Tobo, M; Yamazaki, Y; Watanabe, T; Yagi, M; Sato, M; Suzuki, R; Murooka, H; Sakai, T; Nishitoba, T; Im, DS; Nochi, H; Tamoto, K; Tomura, H; Okajima, F. (2003) Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors. Mol. Pharmacol., 64 (4): 994-1005. [PMID:14500756]
12. Okusa, MD; Ye, H; Huang, L; Sigismund, L; Macdonald, T; Lynch, KR. (2003) Selective blockade of lysophosphatidic acid LPA3 receptors reduces murine renal ischemia-reperfusion injury. Am. J. Physiol. Renal Physiol., 285 (3): F565-74. [PMID:12770838]
13. Simon, MF; Daviaud, D; Pradère, JP; Grès, S; Guigné, C; Wabitsch, M; Chun, J; Valet, P; Saulnier-Blache, JS. (2005) Lysophosphatidic acid inhibits adipocyte differentiation via lysophosphatidic acid 1 receptor-dependent down-regulation of peroxisome proliferator-activated receptor gamma2. J. Biol. Chem., 280 (15): 14656-62. [PMID:15710620]
14. Swaney, JS; Chapman, C; Correa, LD; Stebbins, KJ; Bundey, RA; Prodanovich, PC; Fagan, P; Baccei, CS; Santini, AM; Hutchinson, JH; et al.. (2010) A novel, orally active LPA(1) receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. Br. J. Pharmacol., 160 (7): 1699-713. [PMID:20649573]
15. Virag, T; Elrod, DB; Liliom, K; Sardar, VM; Parrill, AL; Yokoyama, K; Durgam, G; Deng, W; Miller, DD; Tigyi, G. (2003) Fatty alcohol phosphates are subtype-selective agonists and antagonists of lysophosphatidic acid receptors. Mol. Pharmacol., 63 (5): 1032-42. [PMID:12695531]
16. Yanagida, K; Masago, K; Nakanishi, H; Kihara, Y; Hamano, F; Tajima, Y; Taguchi, R; Shimizu, T; Ishii, S. (2009) Identification and characterization of a novel lysophosphatidic acid receptor, p2y5/LPA6. J. Biol. Chem., 284 (26): 17731-41. [PMID:19386608]
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dodecylphosphonic acid, VPC12249 and VPC32179 have antagonist activity at LPA1 and LPA3 receptors [1,12,15]. The selectivity of these antagonists is less than two orders of magnitude. None of the currently available chemical tools have validated specificity in vivo.
Class A orphan receptor LPAR6 is a related lysophospholipid receptor, with the provisional nomenclature LPA6.