Role of the prostanoid EP4 receptor in iloprost-mediated vasodilatation in pulmonary hypertension

American Journal of Respiratory and Critical Care Medicine

Volumn 178, Issue 2, 2008, Pages 188-196

  Lai, Ying Ju ^a   Pullamsetti, Soni Savai ^a,b   Dony, Eva ^a   Weissmann, Norbert ^a   Butrous, Ghazwan ^c   Banat, Gamal Andre ^a   Ghofrani, Hossein Ardeschir ^a   Seeger, Werner ^a   Grimminger, Friedrich ^a   Schermuly, Ralph Theo ^a,b  

^a JUSTUS LIEBIG UNIVERSITY   (Germany)

^b MAX PLANCK INSTITUTE FOR HEART AND LUNG RESEARCH   (Germany)

^c UNIVERSITY OF KENT   (United Kingdom)

Author keywords

Iloprost; Prostanoid EP4 receptor; Pulmonary artery hypertension

Indexed keywords

6 ISOPROPOXY 9 OXO 2 XANTHENECARBOXYLIC ACID; 7 [5 (4 BIPHENYLYLMETHOXY) 2 MORPHOLINO 3 OXOCYCLOPENTYL] 4 HEPTENOIC ACID; CYCLIC AMP; ILOPROST; MESSENGER RNA; MONOCROTALINE; PROSTACYCLIN RECEPTOR; PROSTANOID RECEPTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTERY MUSCLE; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; HUMAN; HUMAN TISSUE; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN ISOLATION; PULMONARY HYPERTENSION; RAT; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA ISOLATION; VASODILATATION;

ANIMALS; CELLS, CULTURED; GENE EXPRESSION REGULATION; HUMANS; HYPERTENSION, PULMONARY; ILOPROST; LUNG; MUSCLE, SMOOTH, VASCULAR; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, EPOPROSTENOL; RECEPTORS, PROSTAGLANDIN E; SIGNAL TRANSDUCTION; VASODILATOR AGENTS;

EID: 46849122659     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.200710-1519OC     Document Type: Article

References (48)

1. Tuder RM, Cool CD, Geraci MW, Wang J, Abman SH, Wright L, Badesch D, Voelkel NF. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med 1999;159:1925-1932.
2. Christman BW, McPherson CD, Newman JH, King GA, Bernard GR, Groves BM, Loyd JE. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med 1992;327:70-75.
3. Giaid A, Yanagisawa M, Langleben D, Michel RP, Levy R, Shennib H, Kimura S, Masaki T, Duguid WP, Stewart DJ. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 1993;328:1732-1739.
4. Eddahibi S, Humbert M, Fadel E, Raffestin B, Darmon M, Capron F, Simonneau G, Dartevelle P, Hamon M, Adnot S. Serotonin transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension. J Clin Invest 2001;108:1141-1150.
5. Marcos E, Fadel E, Sanchez O, Humbert M, Dartevelle P, Simonneau G, Hamon M, Adnot S, Eddahibi S. Serotonin-induced smooth muscle hyperplasia in various forms of human pulmonary hypertension. Circ Res 2004;94:1263-1270.
6. Humbert M, Monti G, Fartoukh M, Magnan A, Brenot F, Rain B, Capron F, Galanaud P, Duroux P, Simonneau G, et al. Platelet-derived growth factor expression in primary pulmonary hypertension: comparison of HIV seropositive and HIV seronegative patients. Eur Respir J 1998;11:554-559.
7. Schermuly RT, Dony E, Ghofrani HA, Pullamsetti S, Savai R, Roth M, Sydykov A, Lai YJ, Weissmann N, Seeger W, et al. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest 2005;115:2811-2821.
8. Wharton J, Strange JW, Moller GM, Growcott EJ, Ren X, Franklyn AP, Phillips SC, Wilkins MR. Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am J Respir Crit Care Med 2005;172:105-113.
9. Schermuly RT, Inholte C, Ghofrani HA, Gall H, Weissmann N, Weidenbach A, Seeger W, Grimminger F. Lung vasodilatory response to inhaled iloprost in experimental pulmonary hypertension: amplification by different type phosphodiesterase inhibitors. Respir Res 2005;6:76.
10. Schermuly RT, Pullamsetti SS, Kwapiszewska G, Dumitrascu R, Tian X, Weissmann N, Ghofrani HA, Kaulen C, Dunkern T, Schudt C, et al. Phosphodiesterase 1 upregulation in pulmonary arterial hypertension:target for reverse-remodeling therapy. Circulation 2007;115:2331-2339.
11. Hoeper MM, Olschewski H, Ghofrani HA, Wilkens H, Winkler J, Borst MM, Niedermeyer J, Fabel H, Seeger W. A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension. German PPH Study Group. J Am Coll Cardiol 2000;35:176-182.
12. Olschewski H, Walmrath D, Schermuly R, Ghofrani A, Grimminger F, Seeger W. Aerosolized prostacyclin and iloprost in severe pulmonary hypertension. Ann Intern Med 1996;124:820-824.
13. Olschewski H, Ghofrani HA, Schmehl T, Winkler J, Wilkens H, Hoper MM, Behr J, Kleber FX, Seeger W. Inhaled iloprost to treat severe pulmonary hypertension: an uncontrolled trial. German PPH Study Group. Ann Intern Med 2000;132:435-443.
14. Olschewski H, Simonneau G, Galie N, Higenbottam T, Naeije R, Rubin LJ, Nikkho S, Speich R, Hoeper MM, Behr J, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 2002;347:322-329.
15. Breyer RM, Bagdassarian CK, Myers SA, Breyer MD. Prostanoid receptors: subtypes and signaling. Annu Rev Pharmacol Toxicol 2001; 41:661-690.
16. Hoshikawa Y, Voelkel NF, Gesell TL, Moore MD, Morris KG, Alger LA, Narumiya S, Geraci MW. Prostacyclin receptor-dependent modulation of pulmonary vascular remodeling. Am J Respir Crit Care Med 2001;164:314-318.
17. Clarke DL, Belvisi MG, Smith SJ, Hardaker E, Yacoub MH, Meja KK, Newton R, Slater DM, Giembycz MA. Prostanoid receptor expression by human airway smooth muscle cells and regulation of the secretion of granulocyte colony-stimulating factor. Am J Physiol Lung Cell Mol Physiol 2005;288:L238-L250.
18. Schermuly RT, Pullamsetti SS, Breitenbach SC, Weissmann N, Ghofrani HA, Grimminger F, Nilius SM, Schror K, Kirchrath JM, Seeger W, et al. Iloprost-induced desensitization of the prostacyclin receptor in isolated rabbit lungs. Respir Res 2007;8:4.
19. Wharton J, Davie N, Upton PD, Yacoub MH, Polak JM, Morrell NW. Prostacyclin analogues differentially inhibit growth of distal and proximal human pulmonary artery smooth muscle cells. Circulation 2000; 102:3130-3136.
20. Narumiya S, Sugimoto Y, Ushikubi F. Prostanoid receptors: structures, properties, and functions. Physiol Rev 1999;79:1193-1226.
21. Fullerton DA, Hahn AR, Banerjee A, Harken AH. Pulmonary vascular smooth muscle relaxation by cGMP- versus cAMP-mediated mechanisms. J Surg Res 1994;57:259-263.
22. Gilman AG. Regulation of adenylyl cyclase by G proteins. Adv Second Messenger Phosphoprotein Res 1990;24:51-57.
23. Pang L, Holland E, Knox AJ. Role of cyclo-oxygenase-2 induction in interleukin-1beta induced attenuation of cultured human airway smooth muscle cell cyclic AMP generation in response to isoprenaline. Br J Pharmacol 1998;125:1320-1328.
24. Iwai N, Katsuya T, Ishikawa K, Mannami T, Ogata J, Higaki J, Ogihara T, Tanabe T, Baba S. Human prostacyclin synthase gene and hypertension: the Suita study. Circulation 1999;100:2231-2236.
25. Geraci MW, Gao B, Shepherd DC, Moore MD, Westcott JY, Fagan KA, Alger LA, Tuder RM, Voelkel NF. Pulmonary prostacyclin synthase overexpression in transgenic mice protects against development of hypoxic pulmonary hypertension. J Clin Invest 1999;103:1509-1515.
26. Schermuly RT, Kreisselmeier KP, Ghofrani HA, Samidurai A, Pullamsetti S, Weissmann N, Schudt C, Ermert L, Seeger W, Grimminger F. Antiremodeling effects of iloprost and the dualselective phosphodiesterase 3/4 inhibitor tolafentrine in chronic experimental pulmonary hypertension. Circ Res 2004;94:1101-1108.
27. Schermuly RT, Yilmaz H, Ghofrani HA, Woyda K, Pullamsetti S, Schulz A, Gessler T, Dumitrascu R, Weissmann N, Grimminger F, et al. Inhaled iloprost reverses vascular remodeling in chronic experimental pulmonary hypertension. Am J Respir Crit Care Med 2005;172:358-363.
28. Itoh T, Nagaya N, Fujii T, Iwase T, Nakanishi N, Hamada K, Kangawa K, Kimura H. A combination of oral sildenafil and beraprost ameliorates pulmonary hypertension in rats. Am J Respir Crit Care Med 2004; 169:34-38.
29. Vane JR, Botting RM. Pharmacodynamic profile of prostacyclin. Am J Cardiol 1995;75:3A-10A.
30. Boie Y, Rushmore TH, Darmon-Goodwin A, Grygorczyk R, Slipetz DM, Metters KM, Abramovitz M. Cloning and expression of a cDNA for the human prostanoid IP receptor. J Biol Chem 1994;269:12173-12178.
31. Coleman RA, Smith WL, Narumiya S. International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes. Pharmacol Rev 1994;46:205-229.
32. Namba T, Oida H, Sugimoto Y, Kakizuka A, Negishi M, Ichikawa A, Narumiya S. cDNA cloning of a mouse prostacyclin receptor: multiple signaling pathways and expression in thymic medulla. J Biol Chem 1994;269:9986-9992.
33. Davis RJ, Murdoch CE, Ali M, Purbrick S, Ravid R, Baxter GS, Tilford N, Sheldrick RL, Clark KL, Coleman RA. EP4 prostanoid receptormediated vasodilatation of human middle cerebral arteries. Br J Pharmacol 2004;141:580-585.
34. Lin CR, Amaya F, Barrett L, Wang H, Takada J, Samad TA, Woolf CJ. Prostaglandin E2 receptor EP4 contributes to inflammatory pain hypersensitivity. J Pharmacol Exp Ther 2006;319:1096-1103.
35. Wilson RJ, Rhodes SA, Wood RL, Shield VJ, Noel LS, Gray DW, Giles H. Functional pharmacology of human prostanoid EP2 and EP4 receptors. Eur J Pharmacol 2004;501:49-58.
36. Wilson RJ, Giles H. Piglet saphenous vein contains multiple relaxatory prostanoid receptors: evidence for EP4, EP2, DP and IP receptor subtypes. Br J Pharmacol 2005;144:405-415.
37. Barst RJ, Rubin LJ, Long WA, McGoon MD, Rich S, Badesch DB, Groves BM, Tapson VF, Bourge RC, Brundage BH. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. The Primary Pulmonary Hypertension Study Group. N Engl J Med 1996;334:296-302.
38. Barst RJ, McGoon M, McLaughlin V, Tapson V, Rich S, Rubin L, Wasserman K, Oudiz R, Shapiro S, Robbins IM, et al. Beraprost therapy for pulmonary arterial hypertension. J Am Coll Cardiol 2003; 41:2119-2125.
39. Rubin LJ, Mendoza J, Hood M, McGoon M, Barst R, Williams WB, Diehl JH, Crow J, Long W. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol): results of a randomized trial. Ann Intern Med 1990;112:485-491.
40. Tuder RM, Zaiman AL. Prostacyclin analogs as the brakes for pulmonary artery smooth muscle cell proliferation: is it sufficient to treat severe pulmonary hypertension? Am J Respir Cell Mol Biol 2002;26: 171-174.
41. Giaid A, Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med 1995;333:214-221.
42. Coggins MP, Bloch KD. Nitric oxide in the pulmonary vasculature. Arterioscler Thromb Vasc Biol 2007;27:1877-1885.
43. Ghofrani HA, Osterloh IH, Grimminger F. Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond. Nat Rev Drug Discov 2006;5:689-702.
44. Dumitrascu R, Weissmann N, Ghofrani HA, Dony E, Beuerlein K, Schmidt H, Stasch JP, Gnoth MJ, Seeger W, Grimminger F, et al. Activation of soluble guanylate cyclase reverses experimental pulmonary hypertension and vascular remodeling. Circulation 2006;113: 286-295.
45. Petkov V, Mosgoeller W, Ziesche R, Raderer M, Stiebellehner L, Vonbank K, Funk GC, Hamilton G, Novotny C, Burian B, et al. Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. J Clin Invest 2003;111:1339-1346.
46. Said SI, Hamidi SA, Dickman KG, Szema AM, Lyubsky S, Lin RZ, Jiang YP, Chen JJ, Waschek JA, Kort S. Moderate pulmonary arterial hypertension in male mice lacking the vasoactive intestinal peptide gene. Circulation 2007;115:1260-1268.
47. Cowan KN, Heilbut A, Humpl T, Lam C, Ito S, Rabinovitch M. Complete reversal of fatal pulmonary hypertension in rats by a serine elastase inhibitor. Nat Med 2000;6:698-702.
48. Clapp LH, Finney P, Turcato S, Tran S, Rubin LJ, Tinker A. Differential effects of stable prostacyclin analogs on smooth muscle proliferation and cyclic AMP generation in human pulmonary artery. Am J Respir Cell Mol Biol 2002;26:194-201.