Knockout mice reveal a role for P2Y6 receptor in macrophages, endothelial cells, and vascular smooth muscle cells

Molecular Pharmacology

Volumn 74, Issue 3, 2008, Pages 777-784

  Bar, Isabelle ^a   Guns, Pieter Jan ^c   Metallo, Jessica ^a   Cammarata, Dorothée ^a   Wilkin, Françoise ^a   Boeynams, Jean Marie ^a,b   Bult, Hidde ^c   Robaye, Bernard ^a,d  

^a UNIVERSITÉ LIBRE DE BRUXELLES   (Belgium)

^b ERASME HOSPITAL   (Belgium)

^c UNIVERSITY OF ANTWERP   (Belgium)

^d NONE   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

INOSITOL PHOSPHATE; INTERLEUKIN 6; LIPOPOLYSACCHARIDE; MACROPHAGE INFLAMMATORY PROTEIN 2; PURINERGIC P2Y6 RECEPTOR; THIOGLYCOLIC ACID; TUMOR NECROSIS FACTOR ALPHA; URIDINE DIPHOSPHATE;

ANIMAL CELL; ANIMAL TISSUE; AORTA; ARTICLE; ATHEROSCLEROSIS; CONTROLLED STUDY; ENDOTHELIUM CELL; GENE TARGETING; HYPERTENSION; KNOCKOUT MOUSE; MACROPHAGE; MOUSE; NONHUMAN; PRIORITY JOURNAL; RECEPTOR INTRINSIC ACTIVITY; SMOOTH MUSCLE RELAXATION; VASCULAR SMOOTH MUSCLE;

ANIMALS; AORTA; CYTOKINES; ENDOTHELIAL CELLS; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; GENE DELETION; GENE EXPRESSION REGULATION; INOSITOL PHOSPHATES; LIPOPOLYSACCHARIDES; MACROPHAGES, PERITONEAL; MAP KINASE SIGNALING SYSTEM; MICE; MICE, KNOCKOUT; MUSCLE CONTRACTION; MUSCLE RELAXATION; MUSCLE, SMOOTH, VASCULAR; MYOCYTES, SMOOTH MUSCLE; NUCLEOTIDES; PHENYLEPHRINE; RECEPTORS, PURINERGIC P2; RNA, MESSENGER; THIOGLYCOLATES; VASOMOTOR SYSTEM;

EID: 50449096581     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.108.046904     Document Type: Article

References (40)

1. Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Knight GE, Fumagalli M, Gachet C, Jacobson KA, et al. (2006) International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol Rev 58:281-341.
2. Boeynaems JM, Communi D, Gonzalez NS, and Robaye B (2005) Overview of the P2 receptors. Semin Thromb Hemost 31:139-149.
3. 2 receptors are coupled to the NO/cGMP pathway to vasodilate the rat arterial mesenteric bed. Br J Pharmacol 136:847-856.
4. Chang K, Hanaoka K, Kumada M, and Takuwa Y (1995) Molecular cloning and functional analysis of a novel P2 nucleotide receptor. J Biol Chem 270:26152-26158.
5. Communi D, Parmentier M, and Boeynaems JM (1996) Cloning, functional expression and tissue distribution of the human P2Y6 receptor. Biochem Biophys Res Commun 222:303-308.
6. Communi D, Raspe E, Pirotton S, and Boeynaems JM (1995) Coexpression of P2Y and P2U receptors on aortic endothelial cells. Comparison of cell localization and signaling pathways. Circ Res 76:191-198.
7. Cox MA, Gomes B, Palmer K, Du K, Wiekowski M, Wilburn B, Petro M, Chou CC, Desquitado C, Schwarz M, et al. (2005) The pyrimidinergic P2Y6 receptor mediates a novel release of proinflammatory cytokines and chemokines in monocytic cells stimulated with UDP. Biochem Biophys Res Commun 330:467-473.
8. Crauwels HM, Van Hove CE, Holvoet P, Herman AG, and Bult H (2003) Plaque-associated endothelial dysfunction in apolipoprotein E-deficient mice on a regular diet. Effect of human apolipoprotein AI. Cardiovasc Res 59:189-199.
9. - transport. J Biol Chem 274:26461-26468.
10. 2+ signaling in macrophages. J Biol Chem 281:35147-35155.
11. Fabre JE, Nguyen M, Latour A, Keifer JA, Audoly LP, Coffman TM, and Koller BH (1999) Decreased platelet aggregation, increased bleeding time and resistance to thromboembolism in P2Y1-deficient mice. Nat Med 5:1199-1202.
12. Foster CJ, Prosser DM, Agans JM, Zhai Y, Smith MD, Lachowicz JE, Zhang FL, Gustafson E, Monsma FJ Jr, Wiekowski MT, et al. (2001) Molecular identification and characterization of the platelet ADP receptor targeted by thienopyridine antithrombotic drugs. J Clin Invest 107:1591-1598.
13. Ghanem E, Robaye B, Leal T, Leipziger J, Van Driessche W, Beauwens R, and Boeynaems JM (2005) The role of epithelial P2Y2 and P2Y4 receptors in the regulation of intestinal chloride secretion. Br J Pharmacol 146:364-369.
14. Guns PJ, Korda A, Crauwels HM, Van Assche T, Robaye B, Boeynaems JM, and Bult H (2005) Pharmacological characterization of nucleotide P2Y receptors on endothelial cells of the mouse aorta. Br J Pharmacol 146:288-295.
15. Guns PJ, Van Assche T, Fransen P, Robaye B, Boeynaems JM, and Bult H (2006) Endothelium-dependent relaxation evoked by ATP and UTP in the aorta of P2Y2-deficient mice. Br J Pharmacol 147:569-574.
16. Hardebo JE, Kåhrström J, Owman C, and Salford LG (1987) Endothelium-dependent relaxation by uridine tri- and diphosphate in isolated human pial vessels. Blood Vessels 24:150-155.
17. Harrington LS, Evans RJ, Wray J, Norling L, Swales KE, Vial C, Ali F, Carrier MJ, and Mitchell JA (2007) Purinergic 2X1 receptors mediate endothelial dependent vasodilation to ATP. Mol Pharmacol 72:1132-1136.
18. Hartley SA, Kato K, Salter KJ, and Kozlowski RZ (1998) Functional evidence for a novel suramin-insensitive pyrimidine receptor in rat small pulmonary arteries. Circ Res 83:940-946.
19. 12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci 9:1512-1519.
20. 6 receptors. Am J Physiol Heart Circ Physiol 282:H784-H792.
21. Koizumi S, Shigemoto-Mogami Y, Nasu-Tada K, Shinozaki Y, Ohsawa K, Tsuda M, Joshi BV, Jacobson KA, Kohsaka S, and Inoue K (2007) UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 446:1091-1095.
22. Köttgen M, Löffler T, Jacobi C, Nitschke R, Pavenstädt H, Schreiber R, Frische S, Nielsen S, and Leipziger J (2003) P2Y6 receptor mediates colonic NaCl secretion via differential activation of cAMP-mediated transport. J Clin Invest 111:371-379.
23. Kukulski F, Ben Yebdri F, Lefebvre J, Warny M, Tessier PA, and Sévigny J (2007) Extracellular nucleotides mediate LPS-induced neutrophil migration in vitro and in vivo. J Leukoc Biol 81:1269-1275.
24. Lazarowski ER, Boucher RC, and Harden TK (2003) Mechanisms of release of nucleotides and integration of their action as P2X- and P2Y-receptor activating molecules. Mol Pharmacol 64:785-795.
25. Lazarowski ER, Paradiso AM, Watt WC, Harden TK, and Boucher RC (1997) UDP activates a mucosal-restricted receptor on human nasal epithelial cells that is distinct from the P2Y2 receptor. Proc Natl Acad Sci U S A 94:2599-2603.
26. 1 receptor-null mice. J Clin Invest 104:1731-1737.
27. Lewis CJ, Ennion SJ, and Evans RJ (2000) P2 purinoceptor-mediated control of rat cerebral (pial) microvasculature; contribution of P2X and P2Y receptors. J Physiol 527:315-324.
28. Malmsjö M, Hou M, Pendergast W, Erlinge D, and Edvinsson L (2003) Potent P2Y6 receptor mediated contractions in human cerebral arteries. BMC Pharmacol 3:4.
29. + secretion activated by luminal P2Y2 and P2Y4 receptors in mouse colon. J Physiol 564:269-279.
30. Motte S, Pirotton S, and Boeynaems JM (1993) Heterogeneity of ATP receptors in aortic endothelial cells. Involvement of P2y and P2u receptors in inositol phosphate response. Circ Res 72:504-510.
31. Robaye B, Ghanem E, Wilkin F, Fokan D, Van Driessche W, Schurmans S, Boeynaems JM, and Beauwens R (2003) Loss of nucleotide regulation of epithelial chloride transport in the jejunum of P2Y4-null mice. Mol Pharmacol 63:777-783.
32. Rubino A, Ziabary L, and Burnstock G (1999) Regulation of vascular tone by UTP and UDP in isolated rat intrapulmonary arteries. Eur J Pharmacol 370:139-143.
33. Somers GR, Hammet FM, Trute L, Southey MC, and Venter DJ (1998) Expression of the P2Y6 purinergic receptor in human T cells infiltrating inflammatory bowel disease. Lab Invest 78:1375-1383.
34. 1 receptor-deficient mice establish the native P2X receptor and a P2Y6-like receptor in arteries. Mol Pharmacol 62:1438-1445.
35. Vonend O, Stegbauer J, Sojka J, Habbel S, Quack I, Robaye B, Boeynaems JM, and Rump LC (2005) Noradrenaline and extracellular nucleotide cotransmission involves activation of vasoconstrictive P2X(1,3)- and P2Y6-like receptors in mouse perfused kidney. Br J Pharmacol 145:66-74.
36. Wang L, Karlsson L, Moses S, Hultgårdh-Nilsson A, Andersson M, Borna C, Gudbjartsson T, Jern S, and Erlinge D (2002) P2 receptor expression profiles in human vascular smooth muscle and endothelial cells. J Cardiovasc Pharmacol 40:841-853.
37. 6 nucleotide receptor mediates monocyte interleukin-8 production in response to UDP or lipopolysaccharide. J Biol Chem 276:26051-26056.
38. Wihlborg AK, Malmsjö M, Eyjolfsson A, Gustafsson R, Jacobson K, and Erlinge D (2003) Extracellular nucleotides induce vasodilatation in human arteries via prostaglandins, nitric oxide and endothelium-derived hyperpolarising factor. Br J Pharmacol 138:1451-1458.
39. Yamamoto K, Sokabe T, Matsumoto T, Yoshimura K, Shibata M, Ohura N, Fukuda T, Sato T, Sekine K, Kato S, et al. (2006) Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice. Nat Med 12:133-137.
40. Zhang P, Li MZ, and Elledge SJ (2002) Toward genetic genome projects: genomic library screening and gene-targeting vector construction in a single step. Nat Genet 30:31-39.