Intercellular lipid mediators and GPCR drug discovery

Biomolecules and Therapeutics

Volumn 21, Issue 6, 2013, Pages 411-422

  Im, Dong Soon ^a  

^a Pusan National University   (South Korea)

Author keywords

Drug discovery; Fatty acid; GPCR; Lipid; Lipid mediator; Lysophospholipid

Indexed keywords

ADENYLATE CYCLASE; AM 095; FATTY ACID; FINGOLIMOD; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR 120; G PROTEIN COUPLED RECEPTOR 40; GPR 183 PROTEIN; GPR 41 PROTEIN; GPR 43 PROTEIN; INTERCELLULAR LIPID MEDIATOR; LIPID; LYSOPHOSPHATIDIC ACID; LYSOPHOSPHATIDIC ACID RECEPTOR; LYSOPHOSPHATIDYLCHOLINE; LYSOPHOSPHATIDYLINOSITOL; LYSOPHOSPHATIDYLSERINE; NEW DRUG; NIBR 0213; PHOSPHOLIPID; SPHINGOSINE 1 PHOSPHATE; UNCLASSIFIED DRUG;

ADAPTIVE IMMUNITY; ALLERGIC ENCEPHALOMYELITIS; AMINO ACID SEQUENCE; APOPTOSIS; CELL MIGRATION; DRUG CLASSIFICATION; DRUG DEVELOPMENT; DRUG EFFICACY; DRUG TARGETING; ENZYME ACTIVATION; FIBROSING ALVEOLITIS; HUMAN; INNATE IMMUNITY; INTERNALIZATION; LIGAND BINDING; MAST CELL DEGRANULATION; MULTIPLE SCLEROSIS; NONHUMAN; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RECEPTOR DOWN REGULATION; REVIEW; SCLERODERMA; SIGNAL TRANSDUCTION; SYSTEMIC SCLEROSIS;

EID: 84888772895     PISSN: 19769148     EISSN: 20054483     Source Type: Journal    
DOI: 10.4062/biomolther.2013.080     Document Type: Review

References (145)

1. Arterburn, J. B., Oprea, T. I., Prossnitz, E. R., Edwards, B. S. and Sk-lar, L. A. (2009) Discovery of selective probes and antagonists for G-protein-coupled receptors FPR/FPRL1 and GPR30. Curr. Top. Med. Chem. 9, 1227-1236.
2. Baker, D., Pryce, G., Davies, W. L. and Hiley, C. R. (2006) In silico patent searching reveals a new cannabinoid receptor. Trends Pharmacol. Sci. 27, 1-4.
3. Benned-Jensen, T. and Rosenkilde, M. M. (2010) Distinct expression and ligand-binding profi les of two constitutively active GPR17 splice variants. Br. J. Pharmacol. 159, 1092-1105.
4. Bratton, D. L. and Henson, P. M. (2008) Apoptotic cell recognition: will the real phosphatidylserine receptor(s) please stand up? Curr. Biol. 18, R76-R79.
5. Bresnick, J. N., Skynner, H. A., Chapman, K. L., Jack, A. D., Zamiara, E., Negulescu, P., Beaumont, K., Patel, S. and McAllister, G. (2003) Identification of signal transduction pathways used by orphan g protein-coupled receptors. Assay Drug Dev. Technol. 1, 239-249.
6. Brink, C., Dahlen, S. E., Drazen, J., Evans, J. F., Hay, D. W., Nicosia, S., Serhan, C. N., Shimizu, T. and Yokomizo, T. (2003) International Union of Pharmacology XXXVII. Nomenclature for leukotriene and lipoxin receptors. Pharmacol. Rev. 55, 195-227.
7. Brink, C., Dahlen, S. E., Drazen, J., Evans, J. F., Hay, D. W., Rovati, G. E., Serhan, C. N., Shimizu, T. and Yokomizo, T. (2004) International Union of Pharmacology XLIV. Nomenclature for the oxoeicosanoid receptor. Pharmacol. Rev. 56, 149-157.
8. Castelino, F. V., Seiders, J., Bain, G., Brooks, S. F., King, C. D., Swaney, J. S., Lorrain, D. S., Chun, J., Luster, A. D. and Tager, A. M. (2011) Amelioration of dermal fibrosis by genetic deletion or pharmacologic antagonism of lysophosphatidic acid receptor 1 in a mouse model of scleroderma. Arthritis Rheum. 63, 1405-1415.
9. Choi, J. W. and Chun, J. (2013) Lysophospholipids and their receptors in the central nervous system. Biochim. Biophys. Acta 1831, 20-32.
10. Chu, Z. L., Carroll, C., Chen, R., Alfonso, J., Gutierrez, V., He, H., Lucman, A., Xing, C., Sebring, K., Zhou, J., Wagner, B., Unett, D., Jones, R. M., Behan, D. P. and Leonard, J. (2010) N-oleoyldo-pamine enhances glucose homeostasis through the activation of GPR119. Mol. Endocrinol. 24, 161-170.
11. Chun, J., Hla, T., Lynch, K. R., Spiegel, S. and Moolenaar, W. H. (2010) International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid receptor nomenclature. Pharmacol. Rev. 62, 579-587.
12. Ciana, P., Fumagalli, M., Trincavelli, M. L., Verderio, C., Rosa, P., Lec-ca, D., Ferrario, S., Parravicini, C., Capra, V., Gelosa, P., Guerrini, U., Belcredito, S., Cimino, M., Sironi, L., Tremoli, E., Rovati, G. E., Martini, C. and Abbracchio, M. P. (2006) The orphan receptor GPR17 identified as a new dual uracil nucleotides/cysteinyl-leukot-rienes receptor. EMBO J. 25, 4615-4627.
13. Coppi, E., Maraula, G., Fumagalli, M., Failli, P., Cellai, L., Bonfanti, E., Mazzoni, L., Coppini, R., Abbracchio, M. P., Pedata, F. and Pug-liese, A. M. (2013) UDP-glucose enhances outward K(+) currents necessary for cell differentiation and stimulates cell migration by activating the GPR17 receptor in oligodendrocyte precursors. Glia 61, 1155-1171.
14. Cork, S. M. and Van Meir, E. G. (2011) Emerging roles for the BAI1 protein family in the regulation of phagocytosis, synaptogenesis, neurovasculature, and tumor development. J. Mol. Med. (Berl) 89, 743-752.
15. Cyster, J. G. and Schwab, S. R. (2012) Sphingosine-1-phosphate and lymphocyte egress from lymphoid organs. Annu. Rev. Immunol. 30, 69-94.
16. Das, S., Owen, K. A., Ly, K. T., Park, D., Black, S. G., Wilson, J. M., Sifri, C. D., Ravichandran, K. S., Ernst, P. B. and Casanova, J. E. (2011) Brain angiogenesis inhibitor 1 (BAI1) is a pattern recognition receptor that mediates macrophage binding and engulfment of Gram-negative bacteria. Proc. Natl. Acad Sci. U.S.A. 108, 2136-2141.
17. Davenport, A. P., Alexander, S. P., Sharman, J. L., Pawson, A. J., Benson, H. E., Monaghan, A. E., Liew, W. C., Mpamhanga, C. P., Bon-ner, T. I., Neubig, R. R., Pin, J. P., Spedding, M. and Harmar, A. J. (2013) International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands. Pharmacol. Rev. 65, 967-986.
18. DiLuigi, A., Weitzman, V. N., Pace, M. C., Siano, L. J., Maier, D. and Mehlmann, L. M. (2008a) Meiotic arrest in human oocytes is maintained by a Gs signaling pathway. Biol. Reprod. 78, 667-672.
19. DiLuigi, A. J., Maier, D. B. and Benadiva, C. A. (2008b) Ruptured ecto-pic pregnancy with contralateral adnexal torsion after spontaneous conception. Fertil. Steril. 90, e1-e3.
20. Dixon, R. A., Kobilka, B. K., Strader, D. J., Benovic, J. L., Dohlman, H. G., Frielle, T., Bolanowski, M. A., Bennett, C. D., Rands, E., Diehl, R. E. and et al. (1986) Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and homology with rhodopsin. Nature 321, 75-79.
21. Duman, J. G., Tzeng, C. P., Tu, Y. K., Munjal, T., Schwechter, B., Ho, T. S. and Tolias, K. F. (2013) The adhesion-GPCR BAI1 regulates synaptogenesis by controlling the recruitment of the Par3/Tiam1 polarity complex to synaptic sites. J. Neurosci. 33, 6964-6978.
22. Eggerickx, D., Denef, J. F., Labbe, O., Hayashi, Y., Refetoff, S., Vas-sart, G., Parmentier, M. and Libert, F. (1995) Molecular cloning of an orphan G-protein-coupled receptor that constitutively activates adenylate cyclase. Biochem. J. 309 (Pt 3), 837-843.
23. Fiorucci, S., Mencarelli, A., Palladino, G. and Cipriani, S. (2009) Bile-acid-activated receptors: targeting TGR5 and farnesoid-X-receptor in lipid and glucose disorders. Trends Pharmacol. Sci. 30, 570-580.
24. Franke, H., Parravicini, C., Lecca, D., Zanier, E. R., Heine, C., Bremicker, K., Fumagalli, M., Rosa, P., Longhi, L., Stocchetti, N., De Simoni, M. G., Weber, M. and Abbracchio, M. P. (2013) Changes of the GPR17 receptor, a new target for neurorepair, in neurons and glial cells in patients with traumatic brain injury. Purinergic Signal. 9, 451-462.
25. Frasch, S. C. and Bratton, D. L. (2012) Emerging roles for lysophos-phatidylserine in resolution of inflammation. Prog. Lipid Res. 51, 199-207.
26. Frasch, S. C., Fernandez-Boyanapalli, R. F., Berry, K. A., Murphy, R. C., Leslie, C. C., Nick, J. A., Henson, P. M. and Bratton, D. L. (2013) Neutrophils regulate tissue Neutrophilia in inflammation via the oxidant-modifi ed lipid lysophosphatidylserine. J. Biol. Chem. 288, 4583-4593.
27. Frasch, S. C., Zemski-Berry, K., Murphy, R. C., Borregaard, N., Hen-son, P. M. and Bratton, D. L. (2007) Lysophospholipids of different classes mobilize neutrophil secretory vesicles and induce redundant signaling through G2A. J. Immunol. 178, 6540-6548.
28. Fredriksson, R., Lagerstrom, M. C., Lundin, L. G. and Schioth, H. B. (2003) The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol. Pharmacol. 63, 1256-1272.
29. Freudzon, L., Norris, R. P., Hand, A. R., Tanaka, S., Saeki, Y., Jones, T. L., Rasenick, M. M., Berlot, C. H., Mehlmann, L. M. and Jaffe, L. A. (2005) Regulation of meiotic prophase arrest in mouse oocytes by GPR3, a constitutive activator of the Gs G protein. J. Cell Biol. 171, 255-265.
30. Goetzl, E. J. (2007) Diverse pathways for nuclear signaling by G protein-coupled receptors and their ligands. FASEB J. 21, 638-642.
31. Gore, V., Patel, P., Chang, C. T., Sivendran, S., Kang, N., Ouedraogo, Y. P., Gravel, S., Powell, W. S. and Rokach, J. (2013) 5-Oxo-ETE receptor antagonists. J. Med. Chem. 56, 3725-3732.
32. Grant, G. E., Rokach, J. and Powell, W. S. (2009) 5-Oxo-ETE and the OXE receptor. Prostaglandins Other Lipid Mediat. 89, 98-104.
33. Grzelczyk, A. and Gendaszewska-Darmach, E. (2013) Novel bioactive glycerol-based lysophospholipids: new data -- new insight into their function. Biochimie 95, 667-679.
34. Guo, Y., Zhang, W., Giroux, C., Cai, Y., Ekambaram, P., Dilly, A. K., Hsu, A., Zhou, S., Maddipati, K. R., Liu, J., Joshi, S., Tucker, S. C., Lee, M. J. and Honn, K. V. (2011) Identification of the orphan G protein-coupled receptor GPR31 as a receptor for 12-(S)-hydroxyeico-satetraenoic acid. J. Biol. Chem. 286, 33832-33840.
35. Hannedouche, S., Zhang, J., Yi, T., Shen, W., Nguyen, D., Pereira, J. P., Guerini, D., Baumgarten, B. U., Roggo, S., Wen, B., Knochen-muss, R., Noel, S., Gessier, F., Kelly, L. M., Vanek, M., Laurent, S., Preuss, I., Miault, C., Christen, I., Karuna, R., Li, W., Koo, D. I., Suply, T., Schmedt, C., Peters, E. C., Falchetto, R., Katopodis, A., Spanka, C., Roy, M. O., Detheux, M., Chen, Y. A., Schultz, P. G., Cho, C. Y., Seuwen, K., Cyster, J. G. and Sailer, A. W. (2011) Oxy-sterols direct immune cell migration via EBI2. Nature 475, 524-527.
36. Hansen, K. B., Rosenkilde, M. M., Knop, F. K., Wellner, N., Diep, T. A., Rehfeld, J. F., Andersen, U. B., Holst, J. J. and Hansen, H. S. (2011) 2-Oleoyl glycerol is a GPR119 agonist and signals GLP-1 release in humans. J. Clin. Endocrinol. Metab. 96, E1409-E1417.
37. Hara, T., Kimura, I., Inoue, D., Ichimura, A. and Hirasawa, A. (2013) Free fatty acid receptors and their role in regulation of energy metabolism. Rev. Physiol. Biochem. Pharmacol. 164, 77-116.
38. Hinckley, M., Vaccari, S., Horner, K., Chen, R. and Conti, M. (2005) The G-protein-coupled receptors GPR3 and GPR12 are involved in cAMP signaling and maintenance of meiotic arrest in rodent oo-cytes. Dev. Biol. 287, 249-261.
39. Hochreiter-Hufford, A. E., Lee, C. S., Kinchen, J. M., Sokolowski, J. D., Arandjelovic, S., Call, J. A., Klibanov, A. L., Yan, Z., Mandell, J. W. and Ravichandran, K. S. (2013) Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion. Nature 497, 263-267.
40. Hosoi, T., Koguchi, Y., Sugikawa, E., Chikada, A., Ogawa, K., Tsuda, N., Suto, N., Tsunoda, S., Taniguchi, T. and Ohnuki, T. (2002) Iden-tification of a novel human eicosanoid receptor coupled to G(i/o) J. Biol. Chem. 277, 31459-31465.
41. Howard, A. D., McAllister, G., Feighner, S. D., Liu, Q., Nargund, R. P., Van der Ploeg, L. H. and Patchett, A. A. (2001) Orphan G-protein-coupled receptors and natural ligand discovery. Trends Pharmacol. Sci. 22, 132-140.
42. Ignatov, A., Lintzel, J., Hermans-Borgmeyer, I., Kreienkamp, H. J., Joost, P., Thomsen, S., Methner, A. and Schaller, H. C. (2003) Role of the G-protein-coupled receptor GPR12 as high-affinity receptor for sphingosylphosphorylcholine and its expression and function in brain development. J. Neurosci. 23, 907-914.
43. Im, D. S. (2002) Orphan G protein-coupled receptors and beyond. Jpn. J. Pharmacol. 90, 101-106.
44. Im, D. S. (2003) Linking Chinese medicine and G-protein-coupled receptors. Trends Pharmacol. Sci. 24, 2-4.
45. Im, D. S. (2004) Discovery of new G protein-coupled receptors for lipid mediators. J. Lipid Res. 45, 410-418.
46. Im, D. S. (2005) Two ligands for a GPCR, proton vs lysolipid. Acta Pharmacol. Sin. 26, 1435-1441.
47. Im, D. S. (2009) New intercellular lipid mediators and their GPCRs: an update. Prostaglandins Other Lipid Mediat. 89, 53-56.
48. Inoue, A., Ishiguro, J., Kitamura, H., Arima, N., Okutani, M., Shuto, A., Higashiyama, S., Ohwada, T., Arai, H., Makide, K. and Aoki, J. (2012) TGFalpha shedding assay: an accurate and versatile method for detecting GPCR activation. Nat. Methods 9, 1021-1029.
49. Irannejad, R., Tomshine, J. C., Tomshine, J. R., Chevalier, M., Ma-honey, J. P., Steyaert, J., Rasmussen, S. G., Sunahara, R. K., El-Samad, H., Huang, B. and von Zastrow, M. (2013) Conformational biosensors reveal GPCR signalling from endosomes. Nature 495, 534-538.
50. Iwashita, M., Makide, K., Nonomura, T., Misumi, Y., Otani, Y., Ishida, M., Taguchi, R., Tsujimoto, M., Aoki, J., Arai, H. and Ohwada, T. (2009) Synthesis and evaluation of lysophosphatidylserine analogues as inducers of mast cell degranulation. Potent activities of lysophosphatidylthreonine and its 2-deoxy derivative. J. Med. Chem. 52, 5837-5863.
51. Jenkins, L., Alvarez-Curto, E., Campbell, K., de Munnik, S., Canals, M., Schlyer, S. and Milligan, G. (2011) Agonist activation of the G protein-coupled receptor GPR35 involves transmembrane domain III and is transduced via Galpha(1)(3) and beta-arrestin-2. Br. J. Pharmacol. 162, 733-748.
52. Johns, D. G., Behm, D. J., Walker, D. J., Ao, Z., Shapland, E. M., Daniels, D. A., Riddick, M., Dowell, S., Staton, P. C., Green, P., Shabon, U., Bao, W., Aiyar, N., Yue, T. L., Brown, A. J., Morrison, A. D. and Douglas, S. A. (2007) The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects. Br. J. Pharmacol. 152, 825-831.
53. Johnson, L. E., Elias, M. S., Bolick, D. T., Skafl en, M. D., Green, R. M. and Hedrick, C. C. (2008) The G protein-coupled receptor G2A: involvement in hepatic lipid metabolism and gallstone formation in mice. Hepatology 48, 1138-1148.
54. Jones, C. E., Holden, S., Tenaillon, L., Bhatia, U., Seuwen, K., Tranter, P., Turner, J., Kettle, R., Bouhelal, R., Charlton, S., Nirmala, N. R., Jarai, G. and Finan, P. (2003) Expression and characterization of a 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid receptor highly expressed on human eosinophils and neutrophils. Mol. Pharmacol. 63, 471-477.
55. Kabarowski, J. H. (2009) G2A and LPC: regulatory functions in immunity. Prostaglandins Other Lipid Mediat. 89, 73-81.
56. Kaur, B., Cork, S. M., Sandberg, E. M., Devi, N. S., Zhang, Z., Klenotic, P. A., Febbraio, M., Shim, H., Mao, H., Tucker-Burden, C., Silver-stein, R. L., Brat, D. J., Olson, J. J. and Van Meir, E. G. (2009) Vas-culostatin inhibits intracranial glioma growth and negatively regulates in vivo angiogenesis through a CD36-dependent mechanism. Cancer Res. 69, 1212-1220.
57. Kawamata, Y., Fujii, R., Hosoya, M., Harada, M., Yoshida, H., Miwa, M., Fukusumi, S., Habata, Y., Itoh, T., Shintani, Y., Hinuma, S., Fu-jisawa, Y. and Fujino, M. (2003) A G protein-coupled receptor responsive to bile acids. J. Biol. Chem. 278, 9435-9440.
58. Kenakin, T. P. (2001) Quantitation in receptor pharmacology. Receptors Channels 7, 371-385.
59. Kitamura, H., Makide, K., Shuto, A., Ikubo, M., Inoue, A., Suzuki, K., Sato, Y., Nakamura, S., Otani, Y., Ohwada, T. and Aoki, J. (2012) GPR34 is a receptor for lysophosphatidylserine with a fatty acid at the sn-2 position. J. Biochem. 151, 511-518.
60. Kohno, M., Hasegawa, H., Inoue, A., Muraoka, M., Miyazaki, T., Oka, K. and Yasukawa, M. (2006) Identification of N-arachidonylglycine as the endogenous ligand for orphan G-protein-coupled receptor GPR18. Biochem. Biophys. Res. Commun. 347, 827-832.
61. Kostenis, E. (2004) A glance at G-protein-coupled receptors for lipid mediators: a growing receptor family with remarkably diverse li-gands. Pharmacol. Ther. 102, 243-257.
62. Lauckner, J. E., Jensen, J. B., Chen, H. Y., Lu, H. C., Hille, B. and Mackie, K. (2008) GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc. Natl. Acad Sci. U. S.A. 105, 2699-2704.
63. Lerner, M. R. (1994) Tools for investigating functional interactions between ligands and G-protein-coupled receptors. Trends Neurosci. 17, 142-146.
64. Liebscher, I., Muller, U., Teupser, D., Engemaier, E., Engel, K. M., Ritscher, L., Thor, D., Sangkuhl, K., Ricken, A., Wurm, A., Piehler, D., Schmutzler, S., Fuhrmann, H., Albert, F. W., Reichenbach, A., Thiery, J., Schoneberg, T. and Schulz, A. (2011) Altered immune response in mice deficient for the G protein-coupled receptor GPR34. J. Biol. Chem. 286, 2101-2110.
65. Liu, C., Yang, X. V., Wu, J., Kuei, C., Mani, N. S., Zhang, L., Yu, J., Sutton, S. W., Qin, N., Banie, H., Karlsson, L., Sun, S. and Loven-berg, T. W. (2011) Oxysterols direct B-cell migration through EBI2. Nature 475, 519-523.
66. Lu, V. B., Puhl, H. L., 3rd and Ikeda, S. R. (2013) N-Arachidonyl gly-cine does not activate G protein-coupled receptor 18 signaling via canonical pathways. Mol. Pharmacol. 83, 267-282.
67. Maekawa, A., Balestrieri, B., Austen, K. F. and Kanaoka, Y. (2009) GPR17 is a negative regulator of the cysteinyl leukotriene 1 receptor response to leukotriene D4. Proc. Natl. Acad Sci. U.S.A. 106, 11685-11690.
68. Maruyama, T., Miyamoto, Y., Nakamura, T., Tamai, Y., Okada, H., Sugiyama, E., Itadani, H. and Tanaka, K. (2002) Identification of membrane-type receptor for bile acids (M-BAR) Biochem. Biophys. Res. Commun. 298, 714-719.
69. Maruyama, T., Tanaka, K., Suzuki, J., Miyoshi, H., Harada, N., Naka-mura, T., Miyamoto, Y., Kanatani, A. and Tamai, Y. (2006) Targeted disruption of G protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) in mice. J. Endocrinol. 191, 197-205.
70. McHugh, D., Hu, S. S., Rimmerman, N., Juknat, A., Vogel, Z., Walker, J. M. and Bradshaw, H. B. (2010) N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor. BMC Neurosci. 11, 44.
71. McHugh, D., Page, J., Dunn, E. and Bradshaw, H. B. (2012) Delta(9) -Tetrahydrocannabinol and N-arachidonyl glycine are full agonists at GPR18 receptors and induce migration in human endometrial HEC-1B cells. Br. J. Pharmacol. 165, 2414-2424.
72. McIntyre, T. M., Pontsler, A. V., Silva, A. R., St Hilaire, A., Xu, Y., Hin-shaw, J. C., Zimmerman, G. A., Hama, K., Aoki, J., Arai, H. and Prestwich, G. D. (2003) Identification of an intracellular receptor for lysophosphatidic acid (LPA): LPA is a transcellular PPARgamma agonist. Proc. Natl. Acad Sci. U.S.A. 100, 131-136.
73. Meyerzu Heringdorf, D. and Jakobs, K. H. (2007) Lysophospholipid receptors: signalling, pharmacology and regulation by lysophos-pholipid metabolism. Biochim. Biophys. Acta 1768, 923-940.
74. Murakami, M., Shiraishi, A., Tabata, K. and Fujita, N. (2008) Identification of the orphan GPCR, P2Y(10) receptor as the sphingosine-1-phosphate and lysophosphatidic acid receptor. Biochem. Biophys. Res. Commun. 371, 707-712.
75. Neetoo-Isseljee, Z., MacKenzie, A. E., Southern, C., Jerman, J., Mc-Iver, E. G., Harries, N., Taylor, D. L. and Milligan, G. (2013) High-throughput identifi cation and characterization of novel, species-selective GPR35 agonists. J. Pharmacol. Exp. Ther. 344, 568-578.
76. Niedernberg, A., Tunaru, S., Blaukat, A., Ardati, A. and Kostenis, E. (2003) Sphingosine 1-phosphate and dioleoylphosphatidic acid are low affinity agonists for the orphan receptor GPR63. Cell. Signal. 15, 435-446.
77. Obinata, H., Hattori, T., Nakane, S., Tatei, K. and Izumi, T. (2005) Iden-tification of 9-hydroxyoctadecadienoic acid and other oxidized free fatty acids as ligands of the G protein-coupled receptor G2A. J. Biol. Chem. 280, 40676-40683.
78. Obinata, H. and Hla, T. (2012) Fine-tuning S1P therapeutics. Chem. Biol. 19, 1080-1082.
79. Obinata, H. and Izumi, T. (2009) G2A as a receptor for oxidized free fatty acids. Prostaglandins Other Lipid Mediat. 89, 66-72.
80. Oh, D.Y., Yoon, J. M., Moon, M. J., Hwang, J. I., Choe, H., Lee, J. Y., Kim, J. I., Kim, S., Rhim, H., O'Dell, D. K., Walker, J. M., Na, H. S., Lee, M. G., Kwon, H. B., Kim, K. and Seong, J. Y. (2008) Iden-tification of farnesyl pyrophosphate and N-arachidonylglycine as endogenous ligands for GPR92. J. Biol. Chem. 283, 21054-21064.
81. Ohishi, T. and Yoshida, S. (2012) The therapeutic potential of GPR119 agonists for type 2 diabetes. Expert Opin. Investig. Drugs 21, 321-328.
82. Oka, S., Nakajima, K., Yamashita, A., Kishimoto, S. and Sugiura, T. (2007) Identification of GPR55 as a lysophosphatidylinositol receptor. Biochem. Biophys. Res. Commun. 362, 928-934.
83. Oka, S., Ota, R., Shima, M., Yamashita, A. and Sugiura, T. (2010) GPR35 is a novel lysophosphatidic acid receptor. Biochem. Bio-phys. Res. Commun. 395, 232-237.
84. Oka, S., Toshida, T., Maruyama, K., Nakajima, K., Yamashita, A. and Sugiura, T. (2009) 2-Arachidonoyl-sn-glycero-3-phosphoinositol: a possible natural ligand for GPR55. J. Biochem. 145, 13-20.
85. Okajima, F. (2013) Regulation of inflammation by extracellular acidi-fication and proton-sensing GPCRs. Cell. Signal. 25, 2263-2271.
86. Overton, H. A., Babbs, A. J., Doel, S. M., Fyfe, M. C., Gardner, L. S., Griffin, G., Jackson, H. C., Procter, M. J., Rasamison, C. M., Tang-Christensen, M., Widdowson, P. S., Williams, G. M. and Reynet, C. (2006) Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab. 3, 167-175.
87. Overton, H. A., Fyfe, M. C. and Reynet, C. (2008) GPR119, a novel G protein-coupled receptor target for the treatment of type 2 diabetes and obesity. Br. J. Pharmacol. 153 Suppl 1, S76-S81.
88. Padmanabhan, S., Myers, A. G. and Prasad, B. M. (2009) Constitu-tively active GPR6 is located in the intracellular compartments. FEBS Lett. 583, 107-112.
89. Park, D., Tosello-Trampont, A. C., Elliott, M. R., Lu, M., Haney, L. B., Ma, Z., Klibanov, A. L., Mandell, J. W. and Ravichandran, K. S. (2007) BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450, 430-434.
90. Parks, B. W., Gambill, G. P., Lusis, A. J. and Kabarowski, J. H. (2005) Loss of G2A promotes macrophage accumulation in atherosclerotic lesions of low density lipoprotein receptor-deficient mice. J. Lipid Res. 46, 1405-1415.
91. Pertwee, R. G., Howlett, A. C., Abood, M. E., Alexander, S. P., Di Marzo, V., Elphick, M. R., Greasley, P. J., Hansen, H. S., Kunos, G., Mackie, K., Mechoulam, R. and Ross, R. A. (2010) International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB(1) and CB(2). Pharmacol. Rev. 62, 588-631.
92. Pineiro, R. and Falasca, M. (2012) Lysophosphatidylinositol signalling: new wine from an old bottle. Biochim. Biophys. Acta 1821, 694-705.
93. Powell, W. S. and Rokach, J. (2013) The eosinophil chemoattractant 5-oxo-ETE and the OXE receptor. Prog. Lipid Res. 52, 651-665.
94. Prossnitz, E. R. and Barton, M. (2009) Signaling, physiological functions and clinical relevance of the G protein-coupled estrogen receptor GPER. Prostaglandins Other Lipid Mediat. 89, 89-97.
95. Prossnitz, E. R. and Barton, M. (2011) The G-protein-coupled estrogen receptor GPER in health and disease. Nat. Rev. Endocrinol. 7, 715-726.
96. Qi, A. D., Harden, T. K. and Nicholas, R. A. (2013) Is GPR17 a P2Y/ leukotriene receptor? Examination of uracil nucleotides, nucleotide sugars, and cysteinyl leukotrienes as agonists of GPR17. J. Pharmacol. Exp. Ther. 347, 38-46.
97. Qin, Y., Verdegaal, E. M., Siderius, M., Bebelman, J. P., Smit, M. J., Leurs, R., Willemze, R., Tensen, C. P. and Osanto, S. (2011) Quantitative expression profi ling of G-protein-coupled receptors (GPCRs) in metastatic melanoma: the constitutively active orphan GPCR GPR18 as novel drug target. Pigment Cell Melanoma Res. 24, 207-218.
98. Quancard, J., Bollbuck, B., Janser, P., Angst, D., Berst, F., Buehl-mayer, P., Streiff, M., Beerli, C., Brinkmann, V., Guerini, D., Smith, P. A., Seabrook, T. J., Traebert, M., Seuwen, K., Hersperger, R., Bruns, C., Bassilana, F. and Bigaud, M. (2012) A potent and selective S1P(1) antagonist with effi cacy in experimental autoimmune encephalomyelitis. Chem. Biol. 19, 1142-1151.
99. Radu, C. G., Nijagal, A., McLaughlin, J., Wang, L. and Witte, O. N. (2005) Differential proton sensitivity of related G protein-coupled receptors T cell death-associated gene 8 and G2A expressed in immune cells. Proc. Natl. Acad. Sci. U.S.A. 102, 1632-1637.
100. Rajagopal, S., Rajagopal, K. and Lefkowitz, R. J. (2010) Teaching old receptors new tricks: biasing seven-transmembrane receptors. Nat. Rev. Drug Discov. 9, 373-386.
101. Ren, H., Orozco, I. J., Su, Y., Suyama, S., Gutierrez-Juarez, R., Hor-vath, T. L., Wardlaw, S. L., Plum, L., Arancio, O. and Accili, D. (2012) FoxO1 target Gpr17 activates AgRP neurons to regulate food intake. Cell 149, 1314-1326.
102. Ritscher, L., Engemaier, E., Staubert, C., Liebscher, I., Schmidt, P., Hermsdorf, T., Rompler, H., Schulz, A. and Schoneberg, T. (2012) The ligand specifi city of the G-protein-coupled receptor GPR34. Biochem. J. 443, 841-850.
103. Rosenkilde, M. M., Benned-Jensen, T., Andersen, H., Holst, P. J., Kledal, T. N., Luttichau, H. R., Larsen, J. K., Christensen, J. P. and Schwartz, T. W. (2006) Molecular pharmacological phenotyping of EBI2. An orphan seven-transmembrane receptor with constitutive activity. J. Biol. Chem. 281, 13199-13208.
104. Ruiz-Medina, J., Ledent, C. and Valverde, O. (2011) GPR3 orphan receptor is involved in neuropathic pain after peripheral nerve injury and regulates morphine-induced antinociception. Neuropharma-cology 61, 43-50.
105. Ryberg, E., Larsson, N., Sjogren, S., Hjorth, S., Hermansson, N. O., Leonova, J., Elebring, T., Nilsson, K., Drmota, T. and Greasley, P. J. (2007) The orphan receptor GPR55 is a novel cannabinoid receptor. Br. J. Pharmacol. 152, 1092-1101.
106. Serhan, C. N., Chiang, N. and Van Dyke, T. E. (2008) Resolving in-flammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat. Rev. Immunol. 8, 349-361.
107. Serhan, C. N., Hong, S., Gronert, K., Colgan, S. P., Devchand, P. R., Mirick, G. and Moussignac, R. L. (2002) Resolvins: a family of bio-active products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinfl ammation signals. J. Exp. Med. 196, 1025-1037.
108. Serhan, C. N., Krishnamoorthy, S., Recchiuti, A. and Chiang, N. (2011) Novel anti-infl ammatory--pro-resolving mediators and their receptors. Curr. Top. Med. Chem. 11, 629-647.
109. Shah, U. and Kowalski, T. J. (2010) GPR119 agonists for the potential treatment of type 2 diabetes and related metabolic disorders. Vi-tam. Horm. 84, 415-448.
110. Sharman, J. L., Mpamhanga, C. P., Spedding, M., Germain, P., Staels, B., Dacquet, C., Laudet, V. and Harmar, A. J. (2011) IUPHAR-DB: new receptors and tools for easy searching and visualization of pharmacological data. Nucleic Acids Res. 39, D534-538.
111. Shukla, A. K., Xiao, K. and Lefkowitz, R. J. (2011) Emerging paradigms of beta-arrestin-dependent seven transmembrane receptor signaling. Trends Biochem. Sci. 36, 457-469.
112. Soga, T., Ohishi, T., Matsui, T., Saito, T., Matsumoto, M., Takasaki, J., Matsumoto, S., Kamohara, M., Hiyama, H., Yoshida, S., Momose, K., Ueda, Y., Matsushime, H., Kobori, M. and Furuichi, K. (2005) Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor. Biochem. Bio-phys. Res. Commun. 326, 744-751.
113. Southern, C., Cook, J. M., Neetoo-Isseljee, Z., Taylor, D. L., Kettle-borough, C. A., Merritt, A., Bassoni, D. L., Raab, W. J., Quinn, E., Wehrman, T. S., Davenport, A. P., Brown, A. J., Green, A., Wiggles-worth, M. J. and Rees, S. (2013) Screening beta-arrestin recruitment for the identification of natural ligands for orphan G-protein-coupled receptors. J. Biomol. Screen. 18, 599-609.
114. Spann, N. J. and Glass, C. K. (2013) Sterols and oxysterols in immune cell function. Nat. Immunol. 14, 893-900.
115. Sugo, T., Tachimoto, H., Chikatsu, T., Murakami, Y., Kikukawa, Y., Sato, S., Kikuchi, K., Nagi, T., Harada, M., Ogi, K., Ebisawa, M. and Mori, M. (2006) Identification of a lysophosphatidylserine receptor on mast cells. Biochem. Biophys. Res. Commun. 341, 1078-1087.
116. Suzuki, M., Takaishi, S., Nagasaki, M., Onozawa, Y., Iino, I., Maeda, H., Komai, T. and Oda, T. (2013) Medium-chain fatty acid-sensing receptor, GPR84, is a proinflammatory receptor. J. Biol. Chem. 288, 10684-10691.
117. Swaney, J. S., Chapman, C., Correa, L. D., Stebbins, K. J., Broad-head, A. R., Bain, G., Santini, A. M., Darlington, J., King, C. D., Baccei, C. S., Lee, C., Parr, T. A., Roppe, J. R., Seiders, T. J., Ziff, J., Prasit, P., Hutchinson, J. H., Evans, J. F. and Lorrain, D. S. (2011) Pharmacokinetic and pharmacodynamic characterization of an oral lysophosphatidic acid type 1 receptor-selective antagonist. J. Pharmacol. Exp. Ther. 336, 693-700.
118. Tabata, K., Baba, K., Shiraishi, A., Ito, M. and Fujita, N. (2007) The orphan GPCR GPR87 was deorphanized and shown to be a ly-sophosphatidic acid receptor. Biochem. Biophys. Res. Commun. 363, 861-866.
119. Talukdar, S., Olefsky, J. M. and Osborn, O. (2011) Targeting GPR120 and other fatty acid-sensing GPCRs ameliorates insulin resistance and infl ammatory diseases. Trends Pharmacol. Sci. 32, 543-550.
120. Tanaka, S., Ishii, K., Kasai, K., Yoon, S. O. and Saeki, Y. (2007) Neural expression of G protein-coupled receptors GPR3, GPR6, and GPR12 up-regulates cyclic AMP levels and promotes neurite outgrowth. J. Biol. Chem. 282, 10506-10515.
121. Tanaka, S., Shaikh, I. M., Chiocca, E. A. and Saeki, Y. (2009) The Gs-linked receptor GPR3 inhibits the proliferation of cerebellar granule cells during postnatal development. PloS one 4, e5922.
122. Thathiah, A., Spittaels, K., Hoffmann, M., Staes, M., Cohen, A., Horre, K., Vanbrabant, M., Coun, F., Baekelandt, V., Delacourte, A., Fisch-er, D. F., Pollet, D., De Strooper, B. and Merchiers, P. (2009) The orphan G protein-coupled receptor 3 modulates amyloid-beta pep-tide generation in neurons. Science 323, 946-951.
123. Thomas, C., Pellicciari, R., Pruzanski, M., Auwerx, J. and Schoonjans, K. (2008) Targeting bile-acid signalling for metabolic diseases. Nat. Rev. Drug Discov. 7, 678-693.
124. Tian, Z., Wang, Y., Zhang, N., Guo, Y. Y., Feng, B., Liu, S. B. and Zhao, M. G. (2013) Estrogen receptor GPR30 exerts anxiolytic effects by maintaining the balance between GABAergic and glutamatergic transmission in the basolateral amygdala of ovariectomized mice after stress. Psychoneuroendocrinology 38, 2218-2233.
125. Tomura, H., Mogi, C., Sato, K. and Okajima, F. (2005) Proton-sensing and lysolipid-sensitive G-protein-coupled receptors: a novel type of multi-functional receptors. Cell. Signal. 17, 1466-1476.
126. Tourino, C., Valjent, E., Ruiz-Medina, J., Herve, D., Ledent, C. and Val-verde, O. (2012) The orphan receptor GPR3 modulates the early phases of cocaine reinforcement. Br. J. Pharmacol. 167, 892-904.
127. Uhlenbrock, K., Gassenhuber, H. and Kostenis, E. (2002) Sphingosine 1-phosphate is a ligand of the human gpr3, gpr6 and gpr12 family of constitutively active G protein-coupled receptors. Cell. Signal. 14, 941-953.
128. Valverde, O., Celerier, E., Baranyi, M., Vanderhaeghen, P., Maldo-nado, R., Sperlagh, B., Vassart, G. and Ledent, C. (2009) GPR3 receptor, a novel actor in the emotional-like responses. PloS one 4, e4704.
129. Vassilatis, D. K., Hohmann, J. G., Zeng, H., Li, F., Ranchalis, J. E., Mortrud, M. T., Brown, A., Rodriguez, S. S., Weller, J. R., Wright, A. C., Bergmann, J. E. and Gaitanaris, G. A. (2003) The G protein-coupled receptor repertoires of human and mouse. Proc. Natl. Acad Sci. U.S.A. 100, 4903-4908.
130. Vassileva, G., Golovko, A., Markowitz, L., Abbondanzo, S. J., Zeng, M., Yang, S., Hoos, L., Tetzloff, G., Levitan, D., Murgolo, N. J., Ke-ane, K., Davis, H. R., Jr., Hedrick, J. and Gustafson, E. L. (2006) Targeted deletion of Gpbar1 protects mice from cholesterol gallstone formation. Biochem. J. 398, 423-430.
131. Venkataraman, C. and Kuo, F. (2005) The G-protein coupled receptor, GPR84 regulates IL-4 production by T lymphocytes in response to CD3 crosslinking. Immunol. Lett. 101, 144-153.
132. Wang, J., Simonavicius, N., Wu, X., Swaminath, G., Reagan, J., Tian, H. and Ling, L. (2006a) Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35. J. Biol. Chem. 281, 22021-22028.
133. Wang, J., Wu, X., Simonavicius, N., Tian, H. and Ling, L. (2006b) Medium-chain fatty acids as ligands for orphan G protein-coupled receptor GPR84. J. Biol. Chem. 281, 34457-34464.
134. Wang, L., Radu, C. G., Yang, L. V., Bentolila, L. A., Riedinger, M. and Witte, O. N. (2005) Lysophosphatidylcholine-induced surface redistribution regulates signaling of the murine G protein-coupled receptor G2A. Mol. Biol. Cell 16, 2234-2247.
135. Watanabe, M., Houten, S. M., Mataki, C., Christoffolete, M. A., Kim, B. W., Sato, H., Messaddeq, N., Harney, J. W., Ezaki, O., Kodama, T., Schoonjans, K., Bianco, A. C. and Auwerx, J. (2006) Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 439, 484-489.
136. Yamashita, A., Oka, S., Tanikawa, T., Hayashi, Y., Nemoto-Sasaki, Y. and Sugiura, T. (2013) The actions and metabolism of lysophos-phatidylinositol, an endogenous agonist for GPR55. Prostaglan-dins Other Lipid Mediat. [Epub ahead of print]
137. Yan, J. J., Jung, J. S., Lee, J. E., Lee, J., Huh, S. O., Kim, H. S., Jung, K. C., Cho, J. Y., Nam, J. S., Suh, H. W., Kim, Y. H. and Song, D. K. (2004) Therapeutic effects of lysophosphatidylcholine in experimental sepsis. Nat. Med. 10, 161-167.
138. Yanagida, K., Kurikawa, Y., Shimizu, T. and Ishii, S. (2013) Current progress in non-Edg family LPA receptor research. Biochim. Bio-phys. Acta 1831, 33-41.
139. Yang, C. R., Wei, Y., Qi, S. T., Chen, L., Zhang, Q. H., Ma, J. Y., Luo, Y. B., Wang, Y. P., Hou, Y., Schatten, H., Liu, Z. H. and Sun, Q. Y. (2012) The G protein coupled receptor 3 is involved in cAMP and cGMP signaling and maintenance of meiotic arrest in porcine oo-cytes. PloS one 7, e38807.
140. Yin, H., Chu, A., Li, W., Wang, B., Shelton, F., Otero, F., Nguyen, D. G., Caldwell, J. S. and Chen, Y. A. (2009) Lipid G protein-coupled receptor ligand identification using beta-arrestin PathHunter assay. J. Biol. Chem. 284, 12328-12338.
141. Yoshida, M., Miyazato, M. and Kangawa, K. (2012) Orphan GPCRs and methods for identifying their ligands. Methods Enzymol. 514, 33-44.
142. Zhang, B. L., Li, Y., Ding, J. H., Dong, F. L., Hou, Y. J., Jiang, B. C., Shi, F. X. and Xu, Y. X. (2012) Sphingosine 1-phosphate acts as an activator for the porcine Gpr3 of constitutively active G protein-coupled receptors. Journal of Zhejiang University. J. Zhejang Univ. Sci. B 13, 555-566.
143. Zhang, R. and Xie, X. (2012) Tools for GPCR drug discovery. Acta Pharmacol. Sin. 33, 372-384.
144. Zhao, P. and Abood, M. E. (2013) GPR55 and GPR35 and their relationship to cannabinoid and lysophospholipid receptors. Life Sci. 92, 453-457.
145. Zhu, T., Gobeil, F., Vazquez-Tello, A., Leduc, M., Rihakova, L., Bosso-lasco, M., Bkaily, G., Peri, K., Varma, D. R., Orvoine, R. and Chem-tob, S. (2006) Intracrine signaling through lipid mediators and their cognate nuclear G-protein-coupled receptors: a paradigm based on PGE2, PAF, and LPA1 receptors. Can. J. Physiol. Pharmacol. 84, 377-391.