Chemical modulators of sphingosine-1-phosphate receptors as barrier-oriented therapeutic molecules

Nature Reviews Drug Discovery

Volumn 8, Issue 4, 2009, Pages 297-307

  Marsolais, David ^a   Rosen, Hugh ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 2 (3 OCTYLPHENYLCARBAMOYL)ETHYL PHOSPHATE; 3 [2 (3 TRIFLUOROMETHYL 4 BIPHENYLYL)BENZO[B]THIEN 5 YLMETHYLAMINO]PROPIONIC ACID; 4 (2,6 DICHLORO 4 PYRIDINYL) 1 (1,3 DIMETHYL 4 ISOPROPYL 1H PYRAZOLO[3,4 B]PYRIDIN 6 YL)SEMICARBAZIDE; 5 (4 PHENYL 5 TRIFLUOROMETHYL 2 THIENYL) 3 (3 TRIFLUOROMETHYLPHENYL) 1,2,4 OXADIAZOLE; CYM 5442; FINGOLIMOD; IMMUNOMODULATING AGENT; SPHINGOSINE 1 PHOSPHATE RECEPTOR; SPHINGOSINE 1 PHOSPHATE RECEPTOR MODULATOR; UNCLASSIFIED DRUG; VPC 44116; W 140; W 146;

ALLERGIC ENCEPHALOMYELITIS; BLOOD BRAIN BARRIER; CELL COMPARTMENTALIZATION; DRUG EFFICACY; DRUG MECHANISM; DRUG SCREENING; DRUG STRUCTURE; DRUG TARGETING; DRUG TRANSPORT; ENDOTHELIUM CELL; GENE ACTIVATION; GENE DELETION; GENE EXPRESSION REGULATION; GENE FUNCTION; HOMEOSTASIS; HUMAN; IMMUNOMODULATION; INFLAMMATORY INFILTRATE; INNATE IMMUNITY; LEUKOCYTE MIGRATION; NONHUMAN; PERMEABILITY BARRIER; PRIORITY JOURNAL; RESPIRATORY DISTRESS; REVIEW;

ANIMALS; CAPILLARY PERMEABILITY; CARDIOVASCULAR SYSTEM; CENTRAL NERVOUS SYSTEM; DRUG DELIVERY SYSTEMS; HUMANS; PHARMACEUTICAL PREPARATIONS; RECEPTORS, LYSOSPHINGOLIPID; SIGNAL TRANSDUCTION;

EID: 64049113731     PISSN: 14741776     EISSN: 14741784     Source Type: Journal    
DOI: 10.1038/nrd2356     Document Type: Review

References (116)

1. de Boer, A. G. & Gaillard, P. J. Blood-brain barrier dysfunction and recovery. J. Neural. Transm. 113, 455-462 (2006).
2. Pardridge, W. M. Blood-brain barrier delivery. Drug Discov. Today 12, 54-61 (2007).
3. Ribatti, D., Nico, B., Crivellato, E. & Artico, M. Development of the blood-brain barrier: A historical point of view. Anat. Rec. B New Anat. 289, 3-8 (2006).
4. Hannun, Y. A., Luberto, C. & Argraves, K. M. Enzymes of sphingolipid metabolism: From modular to integrative signaling. Biochemistry 40, 4893-4903 (2001).
5. Spiegel, S. & Kolesnick, R. Sphingosine 1-phosphate as a therapeutic agent. Leukemia 16, 1596-1602 (2002).
6. Brinkmann, V. Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology. Pharmacol. Ther. 115, 84-105 (2007).
7. Rosen, H., Sanna, M. G., Cahalan, S. M. & Gonzalez-Cabrera, P. J. Tipping the gatekeeper: S1P regulation of endothelial barrier function. Trends Immunol. 28, 102-107 (2007).
8. Rosen, H. & Goetzl, E. J. Sphingosine 1-phosphate and its receptors: An autocrine and paracrine network. Nature Rev. Immunol. 5, 560-570 (2005).
9. Mandala, S. et al. Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science 296, 346-349 (2002).
10. McVerry, B. J. et al. Sphingosine 1-phosphate reduces vascular leak in murine and canine models of acute lung injury. Am. J. Respir. Crit. Care Med. 170, 987-993 (2004).
11. Peng, X. et al. Protective effects of sphingosine 1-phosphate in murine endotoxin-induced inflammatory lung injury. Am. J. Respir. Crit. Care Med. 169, 1245-1251 (2004).
12. Niessen, F. et al. Dendritic cell PAR1-S1P3 signalling couples coagulation and inflammation. Nature 452, 654-658 (2008).
13. Niessen, F. et al. Endogenous EPCR/aPC-PAR1 signaling prevents inflammation-induced vascular leakage and lethality. Blood 13 Jan 2009 (doi: 10.1182/blood-2008-12-192385).
14. Means, C. K. et al. Sphingosine 1-phosphate S1P2 and S1P3 receptor-mediated Akt activation protects against in vivo myocardial ischemia-reperfusion injury. Am. J. Physiol. Heart Circ. Physiol. 292, H2944-H2951 (2007).
15. Awad, A. S. et al. Selective sphingosine 1-phosphate 1 receptor activation reduces ischemia-reperfusion injury in mouse kidney. Am. J. Physiol. Renal Physiol. 290, F1516-F1524 (2006).
16. 1-selective agonist, SEW2871, ameliorates ischemic acute renal failure. Kidney Int. 69, 1601-1608 (2006).
17. Pan, S. et al. A monoselective sphingosine-1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation model. Chem. Biol. 13, 1227-1234 (2006).
18. Shimizu, H. et al. KRP-203, a novel synthetic immunosuppressant, prolongs graft survival and attenuates chronic rejection in rat skin and heart allografts. Circulation 111, 222-229 (2005).
19. Foster, C. A. et al. FTY720 rescue therapy in the dark agouti rat model of experimental autoimmune encephalomyelitis: Expression of central nervous system genes and reversal of blood-brain-barrier damage. Brain Pathol. 4 June 2008 (doi: 10.1111/j.1750-3639.2008.00182.x).
20. Fujino, M. et al. Amelioration of experimental autoimmune encephalomyelitis in Lewis rats by FTY720 treatment. J. Pharmacol. Exp. Ther. 305, 70-77 (2003).
21. Kappos, L. et al. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N. Engl. J. Med. 355, 1124-1140 (2006).
22. Alemany, R., van Koppen, C. J., Danneberg, K., Ter Braak, M. & Meyer Zu Heringdorf, D. Regulation and functional roles of sphingosine kinases. Naunyn Schmiedebergs Arch. Pharmacol. 374, 413-428 (2007).
23. Kihara, A., Anada, Y. & Igarashi, Y. Mouse sphingosine kinase isoforms SPHK1a and SPHK1b differ in enzymatic traits including stability, localization, modification, and oligomerization. J. Biol. Chem. 281, 4532-4539 (2006).
24. Liu, H. et al. Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform. J. Biol. Chem. 275, 19513-19520 (2000).
25. Venkataraman, K. et al. Extracellular export of sphingosine kinase-1a contributes to the vascular S1P gradient. Biochem. J. 397, 461-471 (2006).
26. Billich, A. et al. Phosphorylation of the immunomodulatory drug FTY720 by sphingosine kinases. J. Biol. Chem. 278, 47408-47415 (2003).
27. Chun, J. et al. International Union of Pharmacology. XXXIV. Lysophospholipid receptor nomenclature. Pharmacol. Rev. 54, 265-269 (2002).
28. Uhlenbrock, K., Gassenhuber, H. & Kostenis, E. 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 (2002).
29. Murata, N. et al. Interaction of sphingosine 1-phosphate with plasma components, including lipoproteins, regulates the lipid receptor-mediated actions. Biochem. J. 352, 809-815 (2000).
30. Ito, K. et al. Lack of sphingosine 1-phosphate-degrading enzymes in erythrocytes. Biochem. Biophys. Res. Commun. 357, 212-217 (2007).
31. Hanel, P., Andreani, P. & Graler, M. H. Erythrocytes store and release sphingosine 1-phosphate in blood. FASEB. J. 21, 1202-1209 (2007).
32. Pappu, R. et al. Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science 316, 295-298 (2007).
33. Lee, M. J. et al. Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1. Science 279, 1552-1555 (1998).
34. Lee, M. J. et al. Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate. Cell 99, 301-312 (1999).
35. Liu, Y. et al. Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. J. Clin. Invest. 106, 951-961 (2000).
36. Herr, D. R. et al. Sphingosine 1-phosphate (S1P) signaling is required for maintenance of hair cells mainly via activation of S1P2. J. Neurosci. 27, 1474-1478 (2007).
37. Kono, M. et al. Deafness and stria vascularis defects in S1P2 receptor-null mice. J. Biol. Chem. 282, 10690-10696 (2007).
38. B3/EDG-3. J. Biol. Chem. 277, 25152-25159 (2002).
39. Wei, S. H. et al. Sphingosine 1-phosphate type 1 receptor agonism inhibits transendothelial migration of medullary T cells to lymphatic sinuses. Nature Immunol. 6, 1228-1235 (2005).
40. Sanna, M. G. et al. Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo. Nature Chem. Biol. 2, 434-441 (2006).
41. Foss, F. W. Jr et al. Synthesis and biological evaluation of γ-aminophosphonates as potent, subtype-selective sphingosine 1-phosphate receptor agonists and antagonists. Bioorg. Med. Chem. 15, 663-677 (2007).
42. Garcia, J. G. et al. Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement. J. Clin. Invest. 108, 689-701 (2001).
43. Schaphorst, K. L. et al. Role of sphingosine-1 phosphate in the enhancement of endothelial barrier integrity by platelet-released products. Am. J. Physiol. Lung Cell. Mol. Physiol. 285, L258-L267 (2003).
44. Sanchez, T. et al. Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeability. J. Biol. Chem. 278, 47281-47290 (2003).
45. Guo, Y. et al. Quantitative proteomic analysis of human endothelial cell membrane rafts: Evidence of MARCKS and MRP regulation in the sphingosine 1-phosphate-induced barrier enhancement. Mol. Cell Proteomics 6, 689-696 (2007).
46. Dudek, S. M. et al. Pulmonary endothelial cell barrier enhancement by sphingosine 1-phosphate: Roles for cortactin and myosin light chain kinase. J. Biol. Chem. 279, 24692-24700 (2004).
47. Shikata, Y., Birukov, K. G. & Garcia, J. G. S1P induces FA remodeling in human pulmonary endothelial cells: Role of Rac, GIT1, FAK, and paxillin. J. Appl. Physiol. 94, 1193-1203 (2003).
48. McVerry, B. J. & Garcia, J. G. In vitro and in vivo modulation of vascular barrier integrity by sphingosine 1-phosphate: mechanistic insights. Cell. Signal. 17, 131-139 (2005).
49. Sanchez, T. & Hla, T. Structural and functional characteristics of S1P receptors. J. Cell. Biochem. 92, 913-922 (2004).
50. Sanchez, T. et al. Induction of vascular permeability by the sphingosine-1-phosphate receptor-2 (S1P2R) and its downstream effectors ROCK and PTEN. Arterioscler. Thromb. Vasc. Biol. 27, 1312-1318 (2007).
51. Singleton, P. A. et al. Attenuation of vascular permeability by methylnaltrexone: Role of mOP-R and S1P3 transactivation. Am. J. Respir. Cell Mol. Biol. 37, 222-231 (2007).
52. Singleton, P. A., Dudek, S. M., Ma, S. F. & Garcia, J. G. Transactivation of sphingosine 1-phosphate receptors is essential for vascular barrier regulation. Novel role for hyaluronan and CD44 receptor family. J. Biol. Chem. 281, 34381-34393 (2006).
53. Van Brocklyn, J. R., Behbahani, B. & Lee, N. H. Homodimerization and heterodimerization of S1P/EDG sphingosine-1-phosphate receptors. Biochim. Biophys. Acta 1582, 89-93 (2002).
54. Zaslavsky, A. et al. Homo- and hetero-dimerization of LPA/S1P receptors, OGR1 and GPR4. Biochim. Biophys. Acta 1761, 1200-1212 (2006).
55. Rahaman, M., Costello, R. W., Belmonte, K. E., Gendy, S. S. & Walsh, M. T. Neutrophil sphingosine 1-phosphate and lysophosphatidic acid receptors in pneumonia. Am. J. Respir. Cell Mol. Biol. 34, 233-241 (2006).
56. Skoura, A. et al. Essential role of sphingosine 1-phosphate receptor 2 in pathological angiogenesis of the mouse retina. J. Clin. Invest. 117, 2506-2516 (2007).
57. Yang, A. H., Ishii, I. & Chun, J. In vivo roles of lysophospholipid receptors revealed by gene targeting studies in mice. Biochim. Biophys. Acta 1582, 197-203 (2002).
58. Okazaki, M. et al. Sphingosine 1-phosphate inhibits ischemia reperfusion injury following experimental lung transplantation. Am. J. Transplant. 7, 751-758 (2007).
59. Matthay, M. A. & Zimmerman, G. A. Acute lung injury and the acute respiratory distress syndrome: Four decades of inquiry into pathogenesis and rational management. Am. J. Respir. Cell. Mol. Biol. 33, 319-327 (2005).
60. Ware, L. B. & Matthay, M. A. The acute respiratory distress syndrome. N. Engl. J. Med. 342, 1334-1349 (2000).
61. Bernard, G. R. et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N. Engl. J. Med. 344, 699-709 (2001).
62. Vincent, J. L. et al. Effects of drotrecogin alfa (activated) on organ dysfunction in the PROWESS trial. Crit. Care Med. 31, 834-840 (2003).
63. Liu, K. D. et al. Randomized clinical trial of activated protein C for the treatment of acute lung injury. Am. J. Respir. Crit. Care Med. 178, 618-623 (2008).
64. Dudek, S. M. et al. Pulmonary endothelial cell barrier enhancement by FTY720 does not require the S1P1 receptor. Cell. Signal. 19 1754-1764 (2007).
65. Smith, R. S., Smith, T. J., Blieden, T. M. & Phipps, R. P. Fibroblasts as sentinel cells. Synthesis of chemokines and regulation of inflammation. Am. J. Pathol. 151, 317-322 (1997).
66. Frank, J. A., Wray, C. M., McAuley, D. F., Schwendener, R. & Matthay, M. A. Alveolar macrophages contribute to alveolar barrier dysfunction in ventilator-induced lung injury. Am. J. Physiol. Lung Cell. Mol. Physiol. 291, L1191-L1198 (2006).
67. Peiris, M. Pathogenesis of avian flu H5N1 and SARS. Novartis Found. Symp. 279, 56-60; discussion 60-65, 216-219 (2006).
68. high dendritic cells in homeostasis and in allergic lung inflammation. J. Immunol. 178, 1882-1895 (2007).
69. Lentsch, A. B. & Ward, P. A. Regulation of inflammatory vascular damage. J. Pathol. 190, 343-348 (2000).
70. Pober, J. S. & Min, W. Endothelial cell dysfunction, injury and death. Handb. Exp. Pharmacol. 176, 135-156 (2006).
71. Chatterjee, P. K. Novel pharmacological approaches to the treatment of renal ischemia-reperfusion injury: A comprehensive review. Naunyn Schmiedebergs Arch. Pharmacol. 376, 1-43 (2007).
72. Yilmaz, G. & Granger, D. N. Cell adhesion molecules and ischemic stroke. Neurol. Res. 30, 783-793 (2008).
73. Star, R. A. Treatment of acute renal failure. Kidney Int. 54 1817-1831 (1998).
74. Scalia, R. Statins and the response to myocardial injury. Am. J. Cardiovasc. Drugs 5, 163-170 (2005).
75. Martino, A. et al. Sphingosine 1-phosphate interferes on the differentiation of human monocytes into competent dendritic cells. Scand. J. Immunol. 65, 84-91 (2007).
76. Itagaki, K. & Hauser, C. J. Sphingosine 1-phosphate, a diffusible calcium influx factor mediating store-operated calcium entry. J. Biol. Chem. 278, 27540-27547 (2003).
77. Panetti, T. S., Nowlen, J. & Mosher, D. F. Sphingosine-1-phosphate and lysophosphatidic acid stimulate endothelial cell migration. Arterioscler. Thromb. Vasc. Biol. 20, 1013-1019 (2000).
78. Lan, Y. Y. et al. The sphingosine-1-phosphate receptor agonist FTY720 modulates dendritic cell trafficking in vivo. Am. J. Transplant. 5, 2649-2659 (2005).
79. Zhi, L., Leung, B. P. & Melendez, A. J. Sphingosine kinase 1 regulates pro-inflammatory responses triggered by TNFα in primary human monocytes. J. Cell. Physiol. 208, 109-115 (2006).
80. Lee, C. et al. Attenuation of shock-induced acute lung injury by sphingosine kinase inhibition. J. Trauma 57, 955-960 (2004).
81. Michaud, J., Kohno, M., Proia, R. L. & Hla, T. Normal acute and chronic inflammatory responses in sphingosine kinase 1 knockout mice. FEBS Lett. 580, 4607-4612 (2006).
82. Bolick, D. T. et al. Sphingosine-1-phosphate prevents tumor necrosis factor-mediated monocyte adhesion to aortic endothelium in mice. Arterioscler. Thromb. Vasc. Biol. 25, 976-981 (2005).
83. Whetzel, A. M. et al. Sphingosine-1 phosphate prevents monocyte/ endothelial interactions in type 1 diabetic NOD mice through activation of the S1P1 receptor. Circ. Res. 99, 731-739 (2006).
84. 3. J. Thromb. Haemost. 5, 1292-1301 (2007).
85. Lin, C. I., Chen, C. N., Chen, J. H. & Lee, H. Lysophospholipids increase IL-8 and MCP-1 expressions in human umbilical cord vein endothelial cells through an IL-1-dependent mechanism. J. Cell. Biochem. 99, 1216-1232 (2006).
86. Dev, K. K. et al. Brain sphingosine-1-phosphate receptors: implication for FTY720 in the treatment of multiple sclerosis. Pharmacol. Ther. 117, 77-93 (2008).
87. Noseworthy, J. H., Lucchinetti, C., Rodriguez, M. & Weinshenker, B. G. Multiple sclerosis. N. Engl. J. Med. 343, 938-952 (2000).
88. Rausch, M. et al. Predictability of FTY720 efficacy in experimental autoimmune encephalomyelitis by in vivo macrophage tracking: Clinical implications for ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging. J. Magn. Reson. Imaging 20, 16-24 (2004).
89. Brinkmann, V. et al. The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J. Biol. Chem. 277, 21453-21457 (2002).
90. Foster, C. A. et al. Brain penetration of the oral immunomodulatory drug FTY720 and its phosphorylation in the central nervous system during experimental autoimmune encephalomyelitis: consequences for mode of action in multiple sclerosis. J. Pharmacol. Exp. Ther. 323, 469-475 (2007).
91. Pilorget, A. et al. Modulation of P-glycoprotein function by sphingosine kinase-1 in brain endothelial cells. J. Neurochem. 100, 1203-1210 (2007).
92. Yopp, A. C. et al. Sphingosine 1-phosphate receptors regulate chemokine-driven transendothelial migration of lymph node but not splenic T cells. J. Immunol. 175, 2913-2924 (2005).
93. Singer, I. et al. Sphingosine-1-phosphate agonists increase macrophage homing, lymphocyte contacts, and endothelial junctional complex formation in murine lymph nodes. J. Immunol. 175, 7151-7161 (2005).
94. Webb, M. et al. Sphingosine 1-phosphate receptor agonists attenuate relapsing-remitting experimental autoimmune encephalitis in SJL mice. J. Neuroimmunol. 153, 108-121 (2004).
95. Kataoka, H. et al. FTY720, sphingosine 1-phosphate receptor modulator, ameliorates experimental auto immune encephalomyelitis by inhibition of T cell infiltration. Cell. Mol. Immunol. 2, 439-448 (2005).
96. Lo, E. H., Singhal, A. B., Torchilin, V. P. & Abbott, N. J. Drug delivery to damaged brain. Brain Res. Rev. 38, 140-148 (2001).
97. Prados, M. D. et al. A randomized, double-blind, placebo-controlled, phase 2 study of RMP-7 in combination with carboplatin administered intravenously for the treatment of recurrent malignant glioma. Neuro.Oncol. 5, 96-103 (2003).
98. Warren, K. et al. Phase II trial of intravenous lobradimil and carboplatin in childhood brain tumors: A report from the Children's Oncology Group. Cancer Chemother. Pharmacol. 58, 343-347 (2006).
99. Sanna, M. G. et al. Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate. J. Biol. Chem. 279, 13839-13848 (2004).
100. Tsukada, Y. T., Sanna, M. G., Rosen, H. & Gottlieb, R. A. S1P1-selective agonist SEW2871 exacerbates reperfusion arrhythmias. J. Cardiovasc. Pharmacol. 50, 660-669 (2007).
101. Gonzalez-Cabrera, P. J. et al. Full pharmacological efficacy of a novel S1P1 agonist that does not require S1P-like head-group interactions. Mol. Pharmacol. 15 Aug 2008 (doi:10.1124/ mol.108.049783).
102. Marsolais, D. et al. Local not systemic modulation of dendritic cell S1P receptors in lung blunts virus-specific immune responses to influenza. Mol. Pharmacol. 74, 896-903 (2008).
103. Jo, E. et al. S1P1-selective in vivo-active agonists from high-throughput screening: Off-the-shelf chemical probes of receptor interactions, signaling, and fate. Chem. Biol. 12, 703-715 (2005).
104. 3 by FTY720-phosphate. Cell. Signal. 20, 1125-1133 (2008).
105. Mechtcheriakova, D. et al. FTY720-phosphate is dephosphorylated by lipid phosphate phosphatase 3. FEBS Lett. 581, 3063-3068 (2007).
106. Yatomi, Y., Ruan, F., Hakomori, S. & Igarashi, Y. Sphingosine-1-phosphate: A platelet-activating sphingolipid released from agonist-stimulated human platelets. Blood 86, 193-202 (1995).
107. Mitra, P. et al. Role of ABCC1 in export of sphingosine-1-phosphate from mast cells. Proc. Natl Acad. Sci. USA 103, 16394-16399 (2006).
108. Kawahara, A. et al. The sphingolipid transporter Spns2 functions in migration of zebrafish myocardial precursors. Science 323 524-527 (2008).
109. Le Stunff, H., Peterson, C., Liu, H., Milstien, S. & Spiegel, S. Sphingosine-1-phosphate and lipid phosphohydrolases. Biochim. Biophys. Acta 1582, 8-17 (2002).
110. Levkau, B. Sphingosine-1-phosphate in the regulation of vascular tone: A finely tuned integration system of S1P sources, receptors, and vascular responsiveness. Circ. Res. 103, 231-233 (2008).
111. Roviezzo, F. et al. Sphingosine-1-phosphate/sphingosine kinase pathway is involved in mouse airway hyperresponsiveness. Am. J. Respir. Cell. Mol. Biol. 36, 757-762 (2007).
112. Theilmeier, G. et al. High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor. Circulation 114, 1403-1409 (2006).
113. Tani, M. et al. Sphingosine 1-phosphate (S1P) inhibits monocyte-endothelial cell interaction by regulating of RhoA activity. FEBS Lett. 581, 4621-4626 (2007).
114. Song, J. et al. A novel sphingosine 1-phosphate receptor agonist, 2-amino-2-propanediol hydrochloride (KRP-203), regulates chronic colitis in interleukin-10 gene-deficient mice. J. Pharmacol. Exp. Ther. 324, 276-283 (2008).
115. Davis, M. D., Clemens, J. J., Macdonald, T. L. & Lynch, K. R. Sphingosine 1-phosphate analogs as receptor antagonists. J. Biol. Chem. 280, 9833-9841 (2005).
116. Osada, M., Yatomi, Y., Ohmori, T., Ikeda, H. & Ozaki, Y. Enhancement of sphingosine 1-phosphate-induced migration of vascular endothelial cells and smooth muscle cells by an EDG-5 antagonist. Biochem. Biophys. Res. Commun. 299, 483-487 (2002).