Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Intercellular Lipid Mediators and GPCR Drug Discovery

  • Im, Dong-Soon (Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University)
  • Received : 2013.10.04
  • Accepted : 2013.11.04
  • Published : 2013.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

G-protein-coupled receptors (GPCR) are the largest superfamily of receptors responsible for signaling between cells and tissues, and because they play important physiological roles in homeostasis, they are major drug targets. New technologies have been developed for the identification of new ligands, new GPCR functions, and for drug discovery purposes. In particular, intercellular lipid mediators, such as, lysophosphatidic acid and sphingosine 1-phosphate have attracted much attention for drug discovery and this has resulted in the development of fingolimod (FTY-720) and AM095. The discovery of new intercellular lipid mediators and their GPCRs are discussed from the perspective of drug development. Lipid GPCRs for lysophospholipids, including lysophosphatidylserine, lysophosphatidylinositol, lysophosphatidylcholine, free fatty acids, fatty acid derivatives, and other lipid mediators are reviewed.

Keywords

References

  1. Arterburn, J. B., Oprea, T. I., Prossnitz, E. R., Edwards, B. S. and Sklar, 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. https://doi.org/10.2174/156802609789753608
  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. https://doi.org/10.1016/j.tips.2005.11.003
  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. https://doi.org/10.1111/j.1476-5381.2009.00633.x
  4. Bratton, D. L. and Henson, P. M. (2008) Apoptotic cell recognition: will the real phosphatidylserine receptor(s) please stand up? Curr. Biol. 18, R76-79. https://doi.org/10.1074/jbc.M112.444414
  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) Identifi cation of signal transduction pathways used by orphan g protein-coupled receptors. Assay Drug Dev. Technol. 1, 239-249. https://doi.org/10.1089/15406580360545053
  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. https://doi.org/10.1124/pr.55.1.8
  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. https://doi.org/10.1124/pr.56.1.4
  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. https://doi.org/10.1002/art.30262
  9. Choi, J. W. and Chun, J. (2013) Lysophospholipids and their receptors in the central nervous system. Biochim. Biophys. Acta 1831, 20-32. https://doi.org/10.1016/j.bbalip.2012.07.015
  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-oleoyldopamine enhances glucose homeostasis through the activation of GPR119. Mol. Endocrinol. 24, 161-170. https://doi.org/10.1073/pnas.94.21.11285
  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. https://doi.org/10.1038/368561a0
  12. Ciana, P., Fumagalli, M., Trincavelli, M. L., Verderio, C., Rosa, P., Lecca, 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 identifi ed as a new dual uracil nucleotides/cysteinyl-leukotrienes receptor. EMBO J. 25, 4615-4627. https://doi.org/10.1038/sj.emboj.7601341
  13. Coppi, E., Maraula, G., Fumagalli, M., Failli, P., Cellai, L., Bonfanti, E., Mazzoni, L., Coppini, R., Abbracchio, M. P., Pedata, F. and Pugliese, 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. https://doi.org/10.1002/glia.22506
  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. https://doi.org/10.1007/s00109-011-0759-x
  15. Cyster, J. G. and Schwab, S. R. (2012) Sphingosine-1-phosphate and lymphocyte egress from lymphoid organs. Annu. Rev. Immunol. 30, 69-94. https://doi.org/10.1146/annurev-immunol-020711-075011
  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. https://doi.org/10.1073/pnas.1014775108
  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., Bonner, 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. https://doi.org/10.1124/pr.112.007179
  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. https://doi.org/10.1095/biolreprod.107.066019
  19. DiLuigi, A. J., Maier, D. B. and Benadiva, C. A. (2008b) Ruptured ectopic pregnancy with contralateral adnexal torsion after spontaneous conception. Fertil. Steril. 90, e1-3. https://doi.org/10.1016/j.fertnstert.2007.07.1333
  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. https://doi.org/10.1038/321075a0
  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. https://doi.org/10.1523/JNEUROSCI.3978-12.2013
  22. Eggerickx, D., Denef, J. F., Labbe, O., Hayashi, Y., Refetoff, S., Vassart, 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. https://doi.org/10.1042/bj3090837
  23. Fiorucci, S., Mencarelli, A., Palladino, G. and Cipriani, S. (2009) Bileacid-activated receptors: targeting TGR5 and farnesoid-X-receptor in lipid and glucose disorders. Trends Pharmacol. Sci. 30, 570-580. https://doi.org/10.1016/j.tips.2009.08.001
  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. https://doi.org/10.1007/s11302-013-9366-3
  25. Frasch, S. C. and Bratton, D. L. (2012) Emerging roles for lysophosphatidylserine in resolution of infl ammation. Prog. Lipid Res. 51, 199-207. https://doi.org/10.1016/j.plipres.2012.03.001
  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-modified lipid lysophosphatidylserine. J. Biol. Chem. 288, 4583-4593. https://doi.org/10.1074/jbc.M112.438507
  27. Frasch, S. C., Zemski-Berry, K., Murphy, R. C., Borregaard, N., Henson, 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. https://doi.org/10.4049/jimmunol.178.10.6540
  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. https://doi.org/10.1124/mol.63.6.1256
  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. https://doi.org/10.1083/jcb.200506194
  30. Goetzl, E. J. (2007) Diverse pathways for nuclear signaling by G protein-coupled receptors and their ligands. FASEB J. 21, 638-642. https://doi.org/10.1096/fj.06-6624hyp
  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. https://doi.org/10.1021/jm400480j
  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. https://doi.org/10.1016/j.prostaglandins.2009.05.002
  33. Grzelczyk, A. and Gendaszewska-Darmach, E. (2013) Novel bioactive glycerol-based lysophospholipids: new data--new insight into their function. Biochimie 95, 667-679. https://doi.org/10.1016/j.biochi.2012.10.009
  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) Identifi cation of the orphan G protein-coupled receptor GPR31 as a receptor for 12-(S)-hydroxyeicosatetraenoic acid. J. Biol. Chem. 286, 33832-33840. https://doi.org/10.1074/jbc.M110.216564
  35. Hannedouche, S., Zhang, J., Yi, T., Shen, W., Nguyen, D., Pereira, J. P., Guerini, D., Baumgarten, B. U., Roggo, S., Wen, B., Knochenmuss, 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) Oxysterols direct immune cell migration via EBI2. Nature 475, 524-527. https://doi.org/10.1038/nature10280
  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, E1409-1417. https://doi.org/10.1210/jc.2011-0647
  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. https://doi.org/10.1007/112_2013_13
  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 oocytes. Dev. Biol. 287, 249-261. https://doi.org/10.1016/j.ydbio.2005.08.019
  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. https://doi.org/10.1038/nature12135
  40. Hosoi, T., Koguchi, Y., Sugikawa, E., Chikada, A., Ogawa, K., Tsuda, N., Suto, N., Tsunoda, S., Taniguchi, T. and Ohnuki, T. (2002) Identification of a novel human eicosanoid receptor coupled to G(i/o) J. Biol. Chem. 277, 31459-31465. https://doi.org/10.1074/jbc.M203194200
  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-proteincoupled 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. https://doi.org/10.1254/jjp.90.101
  44. Im, D. S. (2003) Linking Chinese medicine and G-protein-coupled receptors. Trends Pharmacol. Sci. 24, 2-4. https://doi.org/10.1016/S0165-6147(02)00012-3
  45. Im, D. S. (2004) Discovery of new G protein-coupled receptors for lipid mediators. J. Lipid Res. 45, 410-418. https://doi.org/10.1194/jlr.R300006-JLR200
  46. Im, D. S. (2005) Two ligands for a GPCR, proton vs lysolipid. Acta Pharmacol. Sin. 26, 1435-1441. https://doi.org/10.1111/j.1745-7254.2005.00237.x
  47. Im, D. S. (2009) New intercellular lipid mediators and their GPCRs: an update. Prostaglandins Other Lipid Mediat. 89, 53-56. https://doi.org/10.1016/j.prostaglandins.2009.01.002
  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. https://doi.org/10.1038/nmeth.2172
  49. Irannejad, R., Tomshine, J. C., Tomshine, J. R., Chevalier, M., Mahoney, 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. https://doi.org/10.1038/nature12000
  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. https://doi.org/10.1021/jm900598m
  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. https://doi.org/10.1111/j.1476-5381.2010.01082.x
  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. https://doi.org/10.1002/hep.22433
  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. https://doi.org/10.1124/mol.63.3.471
  55. Kabarowski, J. H. (2009) G2A and LPC: regulatory functions in immunity. Prostaglandins Other Lipid Mediat. 89, 73-81. https://doi.org/10.1016/j.prostaglandins.2009.04.007
  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., Silverstein, R. L., Brat, D. J., Olson, J. J. and Van Meir, E. G. (2009) Vasculostatin inhibits intracranial glioma growth and negatively regulates in vivo angiogenesis through a CD36-dependent mechanism. Cancer Res. 69, 1212-1220. https://doi.org/10.1158/0008-5472.CAN-08-1166
  57. Kawamata, Y., Fujii, R., Hosoya, M., Harada, M., Yoshida, H., Miwa, M., Fukusumi, S., Habata, Y., Itoh, T., Shintani, Y., Hinuma, S., Fujisawa, Y. and Fujino, M. (2003) A G protein-coupled receptor responsive to bile acids. J. Biol. Chem. 278, 9435-9440. https://doi.org/10.1074/jbc.M209706200
  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. https://doi.org/10.1093/jb/mvs011
  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. https://doi.org/10.1016/j.bbrc.2006.06.175
  61. Kostenis, E. (2004) A glance at G-protein-coupled receptors for lipid mediators: a growing receptor family with remarkably diverse ligands. Pharmacol. Ther. 102, 243-257. https://doi.org/10.1016/j.pharmthera.2004.04.005
  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. https://doi.org/10.1073/pnas.0711278105
  63. Lerner, M. R. (1994) Tools for investigating functional interactions between ligands and G-protein-coupled receptors. Trends Neurosci. 17, 142-146. https://doi.org/10.1016/0166-2236(94)90087-6
  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. https://doi.org/10.1074/jbc.M110.196659
  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 Lovenberg, T. W. (2011) Oxysterols direct B-cell migration through EBI2. Nature 475, 519-523. https://doi.org/10.1038/nature10226
  66. Lu, V. B., Puhl, H. L., 3rd and Ikeda, S. R. (2013) N-Arachidonyl glycine does not activate G protein-coupled receptor 18 signaling via canonical pathways. Mol. Pharmacol. 83, 267-282. https://doi.org/10.1124/mol.112.081182
  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. https://doi.org/10.1073/pnas.0905364106
  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. https://doi.org/10.1016/S0006-291X(02)02550-0
  69. Maruyama, T., Tanaka, K., Suzuki, J., Miyoshi, H., Harada, N., Nakamura, 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. https://doi.org/10.1677/joe.1.06546
  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. https://doi.org/10.1186/1471-2202-11-44
  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. https://doi.org/10.1111/j.1476-5381.2011.01497.x
  72. McIntyre, T. M., Pontsler, A. V., Silva, A. R., St Hilaire, A., Xu, Y., Hinshaw, 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. https://doi.org/10.1073/pnas.0135855100
  73. Meyer zu Heringdorf, D. and Jakobs, K. H. (2007) Lysophospholipid receptors: signalling, pharmacology and regulation by lysophospholipid metabolism. Biochim. Biophys. Acta 1768, 923-940. https://doi.org/10.1016/j.bbamem.2006.09.026
  74. Murakami, M., Shiraishi, A., Tabata, K. and Fujita, N. (2008) Identifi cation of the orphan GPCR, P2Y(10) receptor as the sphingosine-1-phosphate and lysophosphatidic acid receptor. Biochem. Biophys. Res. Commun. 371, 707-712. https://doi.org/10.1016/j.bbrc.2008.04.145
  75. Neetoo-Isseljee, Z., MacKenzie, A. E., Southern, C., Jerman, J., Mc-Iver, E. G., Harries, N., Taylor, D. L. and Milligan, G. (2013) Highthroughput identifi cation and characterization of novel, speciesselective GPR35 agonists. J. Pharmacol. Exp. Ther. 344, 568-578. https://doi.org/10.1124/jpet.112.201798
  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. https://doi.org/10.1016/S0898-6568(02)00119-5
  77. Obinata, H., Hattori, T., Nakane, S., Tatei, K. and Izumi, T. (2005) Identification 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. https://doi.org/10.1074/jbc.M507787200
  78. Obinata, H. and Hla, T. (2012) Fine-tuning S1P therapeutics. Chem. Biol. 19, 1080-1082. https://doi.org/10.1016/j.chembiol.2012.09.002
  79. Obinata, H. and Izumi, T. (2009) G2A as a receptor for oxidized free fatty acids. Prostaglandins Other Lipid Mediat. 89, 66-72. https://doi.org/10.1016/j.prostaglandins.2008.11.002
  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) Identification of farnesyl pyrophosphate and N-arachidonylglycine as endogenous ligands for GPR92. J. Biol. Chem. 283, 21054-21064. https://doi.org/10.1074/jbc.M708908200
  81. Ohishi, T. and Yoshida, S. (2012) The therapeutic potential of GPR119 agonists for type 2 diabetes. Expert Opin. Investig. Drugs 21, 321-328. https://doi.org/10.1517/13543784.2012.657797
  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. https://doi.org/10.1016/j.bbrc.2007.08.078
  83. Oka, S., Ota, R., Shima, M., Yamashita, A. and Sugiura, T. (2010) GPR35 is a novel lysophosphatidic acid receptor. Biochem. Biophys. Res. Commun. 395, 232-237. https://doi.org/10.1016/j.bbrc.2010.03.169
  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 acidification and proton-sensing GPCRs. Cell. Signal. 25, 2263-2271. https://doi.org/10.1016/j.cellsig.2013.07.022
  86. Overton, H. A., Babbs, A. J., Doel, S. M., Fyfe, M. C., Gardner, L. S., Griffi n, 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. https://doi.org/10.1016/j.cmet.2006.02.004
  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, S76-81.
  88. Padmanabhan, S., Myers, A. G. and Prasad, B. M. (2009) Constitutively active GPR6 is located in the intracellular compartments. FEBS Lett. 583, 107-112. https://doi.org/10.1016/j.febslet.2008.11.033
  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. https://doi.org/10.1038/nature06329
  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. https://doi.org/10.1194/jlr.M500085-JLR200
  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. https://doi.org/10.1124/pr.110.003004
  92. Pineiro, R. and Falasca, M. (2012) Lysophosphatidylinositol signalling: new wine from an old bottle. Biochim. Biophys. Acta 1821, 694-705. https://doi.org/10.1016/j.bbalip.2012.01.009
  93. Powell, W. S. and Rokach, J. (2013) The eosinophil chemoattractant 5-oxo-ETE and the OXE receptor. Prog. Lipid Res. 52, 651-665. https://doi.org/10.1016/j.plipres.2013.09.001
  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. https://doi.org/10.1016/j.prostaglandins.2009.05.001
  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. https://doi.org/10.1038/nrendo.2011.122
  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. https://doi.org/10.1124/jpet.113.207647
  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 profiling 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. https://doi.org/10.1111/j.1755-148X.2010.00781.x
  98. Quancard, J., Bollbuck, B., Janser, P., Angst, D., Berst, F., Buehlmayer, 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. https://doi.org/10.1016/j.chembiol.2012.07.016
  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. https://doi.org/10.1073/pnas.0409415102
  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. https://doi.org/10.1038/nrd3024
  101. Ren, H., Orozco, I. J., Su, Y., Suyama, S., Gutierrez-Juarez, R., Horvath, 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. https://doi.org/10.1016/j.cell.2012.04.032
  102. Ritscher, L., Engemaier, E., Staubert, C., Liebscher, I., Schmidt, P., Hermsdorf, T., Rompler, H., Schulz, A. and Schoneberg, T. (2012) The ligand specificity of the G-protein-coupled receptor GPR34. Biochem. J. 443, 841-850. https://doi.org/10.1042/BJ20112090
  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. https://doi.org/10.1074/jbc.M602245200
  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. Neuropharmacology 61, 43-50. https://doi.org/10.1016/j.neuropharm.2011.02.014
  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 infl ammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat. Rev. Immunol. 8, 349-361. https://doi.org/10.1038/nri2294
  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 bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J. Exp. Med. 196, 1025-1037. https://doi.org/10.1084/jem.20020760
  108. Serhan, C. N., Krishnamoorthy, S., Recchiuti, A. and Chiang, N. (2011) Novel anti-inflammatory--pro-resolving mediators and their receptors. Curr. Top. Med. Chem. 11, 629-647. https://doi.org/10.2174/1568026611109060629
  109. Shah, U. and Kowalski, T. J. (2010) GPR119 agonists for the potential treatment of type 2 diabetes and related metabolic disorders. Vitam. Horm. 84, 415-448. https://doi.org/10.1016/B978-0-12-381517-0.00016-3
  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. https://doi.org/10.1093/nar/gkq1062
  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. https://doi.org/10.1016/j.tibs.2011.06.003
  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. Biophys. Res. Commun. 326, 744-751. https://doi.org/10.1016/j.bbrc.2004.11.120
  113. Southern, C., Cook, J. M., Neetoo-Isseljee, Z., Taylor, D. L., Kettleborough, C. A., Merritt, A., Bassoni, D. L., Raab, W. J., Quinn, E., Wehrman, T. S., Davenport, A. P., Brown, A. J., Green, A., Wigglesworth, M. J. and Rees, S. (2013) Screening beta-arrestin recruitment for the identifi cation of natural ligands for orphan G-proteincoupled receptors. J. Biomol. Screen. 18, 599-609. https://doi.org/10.1177/1087057113475480
  114. Spann, N. J. and Glass, C. K. (2013) Sterols and oxysterols in immune cell function. Nat. Immunol. 14, 893-900. https://doi.org/10.1038/ni.2681
  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. https://doi.org/10.1016/j.bbrc.2006.01.069
  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. https://doi.org/10.1074/jbc.M112.420042
  117. Swaney, J. S., Chapman, C., Correa, L. D., Stebbins, K. J., Broadhead, 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. https://doi.org/10.1124/jpet.110.175901
  118. Tabata, K., Baba, K., Shiraishi, A., Ito, M. and Fujita, N. (2007) The orphan GPCR GPR87 was deorphanized and shown to be a lysophosphatidic acid receptor. Biochem. Biophys. Res. Commun. 363, 861-866. https://doi.org/10.1016/j.bbrc.2007.09.063
  119. Talukdar, S., Olefsky, J. M. and Osborn, O. (2011) Targeting GPR120 and other fatty acid-sensing GPCRs ameliorates insulin resistance and inflammatory diseases. Trends Pharmacol. Sci. 32, 543-550. https://doi.org/10.1016/j.tips.2011.04.004
  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. https://doi.org/10.1074/jbc.M700911200
  121. Tanaka, S., Shaikh, I. M., Chiocca, E. A. and Saeki, Y. (2009) The Gslinked receptor GPR3 inhibits the proliferation of cerebellar granule cells during postnatal development. PloS one 4, e5922. https://doi.org/10.1371/journal.pone.0005922
  122. Thathiah, A., Spittaels, K., Hoffmann, M., Staes, M., Cohen, A., Horre, K., Vanbrabant, M., Coun, F., Baekelandt, V., Delacourte, A., Fischer, D. F., Pollet, D., De Strooper, B. and Merchiers, P. (2009) The orphan G protein-coupled receptor 3 modulates amyloid-beta peptide generation in neurons. Science 323, 946-951. https://doi.org/10.1126/science.1160649
  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. https://doi.org/10.1038/nrd2619
  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. https://doi.org/10.1016/j.psyneuen.2013.04.011
  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. https://doi.org/10.1016/j.cellsig.2005.06.002
  126. Tourino, C., Valjent, E., Ruiz-Medina, J., Herve, D., Ledent, C. and Valverde, O. (2012) The orphan receptor GPR3 modulates the early phases of cocaine reinforcement. Br. J. Pharmacol. 167, 892-904. https://doi.org/10.1111/j.1476-5381.2012.02043.x
  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. https://doi.org/10.1016/S0898-6568(02)00041-4
  128. Valverde, O., Celerier, E., Baranyi, M., Vanderhaeghen, P., Maldonado, R., Sperlagh, B., Vassart, G. and Ledent, C. (2009) GPR3 receptor, a novel actor in the emotional-like responses. PloS one 4, e4704. https://doi.org/10.1371/journal.pone.0004704
  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 proteincoupled receptor repertoires of human and mouse. Proc. Natl. Acad Sci. U.S.A. 100, 4903-4908. https://doi.org/10.1073/pnas.0230374100
  130. Vassileva, G., Golovko, A., Markowitz, L., Abbondanzo, S. J., Zeng, M., Yang, S., Hoos, L., Tetzloff, G., Levitan, D., Murgolo, N. J., Keane, 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. https://doi.org/10.1042/BJ20060537
  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. https://doi.org/10.1016/j.imlet.2005.05.010
  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. https://doi.org/10.1074/jbc.M603503200
  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. https://doi.org/10.1074/jbc.M608019200
  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. https://doi.org/10.1091/mbc.E04-12-1044
  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. https://doi.org/10.1038/nature04330
  136. Yamashita, A., Oka, S., Tanikawa, T., Hayashi, Y., Nemoto-Sasaki, Y. and Sugiura, T. (2013) The actions and metabolism of lysophosphatidylinositol, an endogenous agonist for GPR55. Prostaglandins 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. https://doi.org/10.1038/nm989
  138. Yanagida, K., Kurikawa, Y., Shimizu, T. and Ishii, S. (2013) Current progress in non-Edg family LPA receptor research. Biochim. Biophys. Acta 1831, 33-41. https://doi.org/10.1016/j.bbalip.2012.08.003
  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 oocytes. PloS one 7, e38807. https://doi.org/10.1371/journal.pone.0038807
  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 identifi cation using beta-arrestin PathHunter assay. J. Biol. Chem. 284, 12328-12338. https://doi.org/10.1074/jbc.M806516200
  141. Yoshida, M., Miyazato, M. and Kangawa, K. (2012) Orphan GPCRs and methods for identifying their ligands. Methods Enzymol. 514, 33-44. https://doi.org/10.1016/B978-0-12-381272-8.00002-7
  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 proteincoupled receptors. Journal of Zhejiang University. J. Zhejang Univ. Sci. B 13, 555-566. https://doi.org/10.1631/jzus.B1100353
  143. Zhang, R. and Xie, X. (2012) Tools for GPCR drug discovery. Acta Pharmacol. Sin. 33, 372-384. https://doi.org/10.1038/aps.2011.173
  144. Zhao, P. and Abood, M. E. (2013) GPR55 and GPR35 and their relationship to cannabinoid and lysophospholipid receptors. Life Sci. 92, 453-457. https://doi.org/10.1016/j.lfs.2012.06.039
  145. Zhu, T., Gobeil, F., Vazquez-Tello, A., Leduc, M., Rihakova, L., Bossolasco, M., Bkaily, G., Peri, K., Varma, D. R., Orvoine, R. and Chemtob, 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. https://doi.org/10.1139/y05-147

Cited by

  1. The emerging pharmacology and function of GPR35 in the nervous system vol.113, 2017, https://doi.org/10.1016/j.neuropharm.2015.07.035
  2. Understanding the local actions of lipids in bone physiology vol.59, 2015, https://doi.org/10.1016/j.plipres.2015.06.002
  3. Translational research on autotaxin-LPA-LPA receptors and drug discovery vol.10, pp.2, 2015, https://doi.org/10.2217/clp.15.4
  4. Functions of omega-3 fatty acids and FFA4 (GPR120) in macrophages vol.785, 2016, https://doi.org/10.1016/j.ejphar.2015.03.094
  5. Proteomic responses of European flounder to temperature and hypoxia as interacting stressors: Differential sensitivities of populations vol.586, 2017, https://doi.org/10.1016/j.scitotenv.2017.02.068
  6. 1,3-dichloro-2-propanol induced lipid accumulation in HepG2 cells through cAMP/protein kinase A and AMP-activated protein kinase pathways via Gi/o-coupled receptors vol.55, 2017, https://doi.org/10.1016/j.etap.2017.07.013
  7. Sphingosine 1-Phosphate Receptor Modulators and Drug Discovery vol.25, pp.1, 2017, https://doi.org/10.4062/biomolther.2016.160
  8. The Regulatory Role of Activating Transcription Factor 2 in Inflammation vol.2014, 2014, https://doi.org/10.1155/2014/950472
  9. Ligand chain length drives activation of lipid G protein-coupled receptors vol.7, pp.1, 2017, https://doi.org/10.1038/s41598-017-02104-5
  10. Structure–Activity Relationships of Lysophosphatidylserine Analogs as Agonists of G-Protein-Coupled Receptors GPR34, P2Y10, and GPR174 vol.58, pp.10, 2015, https://doi.org/10.1021/jm5020082
  11. Regulation of DNA damage repair and lipid uptake by CX3CR1 in epithelial ovarian carcinoma vol.7, pp.5, 2018, https://doi.org/10.1038/s41389-018-0046-6
  12. FFA4 (GPR120) as a fatty acid sensor involved in appetite control, insulin sensitivity and inflammation regulation vol.64, pp.None, 2013, https://doi.org/10.1016/j.mam.2017.09.001
  13. Ginkgolic Acid is a Multi-Target Inhibitor of Key Enzymes in Pro-Inflammatory Lipid Mediator Biosynthesis vol.10, pp.None, 2013, https://doi.org/10.3389/fphar.2019.00797
  14. Lysophosphatidylinositol‐acyltransferase‐1 is involved in cytosolic Ca2+ oscillations in macrophages vol.24, pp.5, 2019, https://doi.org/10.1111/gtc.12681
  15. Gut microbiota confers host resistance to obesity by metabolizing dietary polyunsaturated fatty acids vol.10, pp.1, 2013, https://doi.org/10.1038/s41467-019-11978-0
  16. Spatiotemporal dynamic monitoring of fatty acid–receptor interaction on single living cells by multiplexed Raman imaging vol.117, pp.7, 2013, https://doi.org/10.1073/pnas.1916238117
  17. The impact of ageing on lipid-mediated regulation of adult stem cell behavior and tissue homeostasis vol.189, pp.None, 2020, https://doi.org/10.1016/j.mad.2020.111278
  18. Inhibition of store-operated calcium channels by N-arachidonoyl glycine (NAGly): no evidence for the involvement of lipid-sensing G protein coupled receptors vol.10, pp.None, 2013, https://doi.org/10.1038/s41598-020-59565-4
  19. Development of Free Fatty Acid Receptor 4 (FFA4/GPR120) Agonists in Health Science vol.29, pp.1, 2013, https://doi.org/10.4062/biomolther.2020.213
  20. Foam Cell Macrophages in Tuberculosis vol.12, pp.None, 2013, https://doi.org/10.3389/fimmu.2021.775326
  21. 2-Arachidonyl-lysophosphatidylethanolamine Induces Anti-Inflammatory Effects on Macrophages and in Carrageenan-Induced Paw Edema vol.22, pp.9, 2013, https://doi.org/10.3390/ijms22094865
  22. FFAR4: A New Player in Cardiometabolic Disease? vol.162, pp.8, 2021, https://doi.org/10.1210/endocr/bqab111
  23. G-protein-coupled receptor P2Y10 facilitates chemokine-induced CD4 T cell migration through autocrine/paracrine mediators vol.12, pp.1, 2013, https://doi.org/10.1038/s41467-021-26882-9