KMUP-1 inhibits pulmonary artery proliferation by targeting serotonin receptors/transporter and NO synthase, inactivating RhoA and suppressing AKT/ERK phosphorylation

Vascular Pharmacology

Volumn 53, Issue 5-6, 2010, Pages 239-249

  Chung, Hui Hsuan ^a   Dai, Zen Kong ^a   Wu, Bin Nan ^a   Yeh, Jwu Lai ^a   Chai, Chee Yin ^a   Chu, Koung Shing ^a   Liu, Chung Pin ^a,b   Chen, Ing Jun ^a  

^a KAOHSIUNG MEDICAL UNIVERSITY   (Taiwan)

^b Yens General Hospital   (Taiwan)

Author keywords

5 HT receptor; 5 HTT; AKT; ERK1 2; RhoA

Indexed keywords

4 (1 AMINOETHYL) N (4 PYRIDYL)CYCLOHEXANECARBOXAMIDE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; KMUP 1; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MONOCROTALINE; N(G) NITROARGININE METHYL ESTER; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN; SEROTONIN; SEROTONIN 2A RECEPTOR; SEROTONIN 2B RECEPTOR; SEROTONIN 2C RECEPTOR; SIMVASTATIN; UNCLASSIFIED DRUG; XANTHINE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; CALCIUM CELL LEVEL; CALCIUM TRANSPORT; CELL MIGRATION; CELL PROLIFERATION; DRUG INHIBITION; ENDOTHELIUM CELL; HUMAN; HUMAN CELL; IC 50; LIGAND BINDING; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PULMONARY ARTERIAL SMOOTH MUSCLE CELLS; PULMONARY ARTERY; RAT; SINGLE DRUG DOSE; SMOOTH MUSCLE FIBER; THERAPY EFFECT;

ANIMALS; CELL PROLIFERATION; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; HUMANS; MALE; MONOCROTALINE; MYOCYTES, SMOOTH MUSCLE; NITRIC OXIDE SYNTHASE; PHOSPHORYLATION; PIPERIDINES; PROTO-ONCOGENE PROTEINS C-AKT; PULMONARY ARTERY; RATS; RATS, WISTAR; RECEPTORS, SEROTONIN; RHO-ASSOCIATED KINASES; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; XANTHINES;

EID: 78349304473     PISSN: 15371891     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.vph.2010.09.003     Document Type: Article

References (50)

1. Abe K., Shimokawa H., Morikawa K., Uwatoku T., Oi K., Matsumoto Y., Hattori T., Nakashima Y., Kaibuchi K., Sueishi K., Takeshit A. Long-term treatment with a Rho-kinase inhibitor improves monocrotaline-induced fatal pulmonary hypertension in rats. Circ. Res. 2004, 94:385-393.
2. Barst R.J. PDGF signaling in pulmonary arterial hypertension. J. Clin. Invest. 2005, 115:2691-2694.
3. Black S.M., DeVol J.M., Wedgwood S. Regulation of fibroblast growth factor-2 expression in pulmonary arterial smooth muscle cells involves increased reactive oxygen species generation. Am. J. Physiol. Cell Physiol. 2008, 294:C345-C354.
4. Blanpain C., Poul E.L., Parma J., Knoop C., Detheux M., Parmentier M., Vassart G., Abramowicz M.J. Serotonin 5-HT(2B) receptor loss of function mutation in a patient with fenfluramine-associated primary pulmonary hypertension. Cardiovasc. Res. 2003, 60:518-528.
5. Bonhaus D.W., Stefanich E., Loury D.N., Hsu S.A., Eglen R.M., Wong E.H. Allosteric interactions among agonists and antagonists at 5-hydroxytryptamine3 receptors. J. Neurochem. 1995, 65:104-110.
6. Budzyn, K.; Marley, P.D.; Sobey, C.G., 2004. Chronic mevastatin modulates receptor-dependent vascular contraction in eNOS-deficient mice. Am. J. Physiol. 28 Regul. Integr. Comp. Physiol. 287, R342-348.
7. Callebert J., Esteve J.M., Hervé P., Peoc'h K., Tournois C., Drouet L., Launay J.M., Maroteaux L. Evidence for a control of plasma serotonin levels by 5-hydroxytryptamine (2B) receptors in mice. J. Pharmacol. Exp. Ther. 2006, 317:724-731.
8. Cheng H.C. The power issue: determination of KB or Ki from IC50. A closer look at the Cheng-Prusoff equation, the Schild plot and related power equations. J. Pharmacol. Toxicol. Methods 2001, 46:61-71.
9. Chung H.H., Zen K.D., Wu B.N., Yeh J.L., Chai C.Y., Chu K.S., Liu C.P., Chen I.J. KMUP-1 inhibits acute and chronic pulmonary artery hypertension via eNOS-enhancement and cGMP-dependent inhibition of RhoA/Rho Kinase. Br. J. Pharmacol. 2010, 160:971-986.
10. Crespo M.J., Quidgley J.A. Statins decrease serotonin-induced contractions in coronary arteries of swine in vitro. Pharmacology 2006, 76:141-147.
11. Dempsi Y., MacLean M.R. Pulmonary hypertension: therapeutic targets within the serotonin system. Br. J. Pharmacol. 2008, 155:455-462.
12. Ducret T., Guibert C., Marthan R., Savineau J.P. Serotonin-induced activation of TRPV4-like current in rat intrapulmonary arterial smooth muscle cells. Cell Calcium 2008, 43:315-323.
13. Eddahibi S., Fabre V., Boni C., Martres M.P., Raffestin B., Hamon M., Adnot S. Induction of serotonin transporter by hypoxia in pulmonary vascular smooth muscle cells relationship with the mitogenic action of serotonin. Circ. Res. 1999, 84:329-336.
14. 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.
15. Glusa E., Pertz H.H. Further evidence that 5-HT-induced relaxation of pig pulmonary artery is mediated by endothelial 5-HT(2B) receptors. Br. J. Pharmacol. 2000, 130:692-698.
16. Glusa E., Richiter M. Endothelium-dependent relaxation of porcine pulmonary arteries via 5-HT1C-like receptors. Naunyn-Schmiedeberg's Arch. Pharmacol. 1993, 347:471-477.
17. 2+ entry in human pulmonary artery myocytes during proliferation. Am. J. Physiol. Heart Circ. Physiol. 2001, 280:H746-H755.
18. 2+ sensitization of smooth muscle. J. Biol. Chem. 1997, 272:10704-10709.
19. 2+-sequestering properties in skeletal muscle in chronic obstructive pulmonary disease. Am. J. Physiol. Cell Physiol. 2008, 295:C350-C357.
20. Guibert C., Marthan R., Savineau J.P. Modulation of ion channels in pulmonary arterial hypertension. Curr. Pharm. Des. 2007, 13:2443-2455.
21. Guignabert C., Raffestin B., Benferhat R., Raoul W., Zadigue P., Rideau D., Hamon M., Adnot S., Eddahibi S. Serotonin transporter inhibition prevents and reverses monocrotaline-induced pulmonary hypertension in rats. Circulation 2005, 111:2812-2819.
22. Guilluy C., Rolli-Derkinderen M., Tharaux P.L., Melino G., Pacaud P., Loirand G. Transglutaminase-dependent RhoA activation and depletion by serotonin in vascular smooth muscle cells. J. Biol. Chem. 2007, 282:2918-2928.
23. Guilluy C., Eddahibi S., Agard C., Guignabert C., Izikki M., Tu L., Savale L., Humbert M., Fadel E., Adnot S., Loirand G., Pacaud P. RhoA and Rho kinase activation in human pulmonary hypertension: role of 5-HT signaling. Am. J. Respir. Crit. Care Med. 2009, 179:1151-1158.
24. Hosoda Y., Kanai Y. Role of serotonin in the progression of pulmonary hypertension. Rinsho Ketsueki. 1994, 35:376-380.
25. Hu Y.F., Chen Y.C., Cheng C.C., Higa S., Chen Y.J., Chen S.A. Fluvastatin reduces pulmonary vein spontaneous activity through nitric oxide pathway. J. Cardiovasc. Electrophysiol. 2009, 20:200-206.
26. Kanai Y., Hori S., Tanaka T., Yasuoka M., Watanabe K., Aikawa N., Hosoda Y. Role of 5-hydroxytryptamine in the progression of monocrotaline induced pulmonary hypertension in rats. Cardiovasc. Res. 1993, 27:1619-1623.
27. Kereveur A., Callebert J., Humbert M., Hervé P., Simonneau G., Launay J.M., Drouet L. High plasma serotonin levels in primary pulmonary hypertension: effect of long-term epoprostenol (Prostacyclin) therapy. Arterioscler. Thromb. Vasc. Biol. 2000, 20:2233-2239.
28. 2+ mobilizing properties in migrating endothelial cells. Am. J. Physiol. Heart Circ. Physiol. 2001, 281:H745-H754.
29. Laudi S., Trump S., Schmitz V., West J., McMurtry I.F., Mutlak H., Christians U., Weimann J., Kaisers U., Steudel W. Serotonin transporter protein in pulmonary hypertensive rats treated with atorvastatin. Am. J. Physiol. Lung Cell. Mol. Physiol. 2007, 293:L630-L638.
30. Lee S.L., Wang W.W., Lanzillo J.J., Fanburg B.L. Dual effect of serotonin on growth of bovine pulmonary artery smooth muscle cells in culture. Circ. Res. 1991, 68:1362-1368.
31. Lee S.L., Wang W.W., Lanzillo J.J., Fanburg B.L. Regulation of serotonininduced DNA synthesis of bovine pulmonary artery smooth muscle cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 1994, 266:L53-L60.
32. 2 signals 5-HT-induced ERK MAP kinase activation and mitogenesis of smooth muscle cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 2001, 281:L646-L652.
33. Li M., Li Z., Sun X. Statins suppress MMP2 secretion via inactivation of RhoA/ROCK pathway in pulmonary vascular smooth muscles cells. Eur. J. Pharmacol. 2008, 591:219-223.
34. Liu Y., Fanburg B.L. Serotonin-induced growth of pulmonary artery smooth muscle requires activation of phosphatidylinositol 3-kinase/serine-threonine protein kinase B/mammalian target of rapamycin/p70 ribosomal S6 kinase 1. Am. J. Respir. Cell Mol. Biol. 2006, 34:182-191.
35. Liu Y., Suzuki Y.J., Day R.M., Fanburg B.L. Rho kinase-induced nuclear translocation of ERK1/ERK2 in smooth muscle cell mitogenesis caused by serotonin. Circ. Res. 2004, 95:579-586.
36. MacLean M.R. Pulmonary hypertension, anorexigens and 5-hydroxytryptamine: pharmacological synergism in action?. Trends Pharmacol. Sci. 1999, 20:490-495.
37. MacLean M.R., Herve P., Eddahibi S., Adnot S. 5-Hydroxytryptamine and the pulmonary circulation: receptors, transporters and relevance to pulmonary arterial hypertension. Br. J. Pharmacol. 2000, 131:161-168.
38. MacLean M.R., Deuchar G.A., Hicks M.N., Morecroft I., Shen S., Sheward J., Colston J., Loughlin L., Nilsen M., Dempsie Y., Harmar A. Overexpression of the 5-hydroxytryptamine transporter gene: effect on pulmonary hemodynamics and hypoxia-induced pulmonary hypertension. Circulation 2004, 109:2150-2155.33.
39. Mair K.M., MacLean M.R., Morecroft I., Dempsie Y., Palmer T.M. Novel interactions between the 5-HT transporter, 5-HT1B receptors and Rho kinase in vivo and in pulmonary fibroblasts. Br. J. Pharmacol. 2008, 55(4):606-616.
40. 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.
41. Mauban J.R., Remillard C.V., Yuan J.X. Hypoxic pulmonary vasoconstriction: role of ion channels. J. Appl. Physiol. 2005, 98:415-420.
42. Miyata M., Ito M., Sasajima T., Ohira H., Sato Y., Kasukawa R. Development of monocrotaline-induced pulmonary hypertension is attenuated by a serotonin receptor antagonist. Lung 2000, 178:63-73.
43. Niwano K., Arai M., Tomaru K., Uchiyama T., Ohyama Y., Kurabayashi M. Transcriptional stimulation of the eNOS gene by the stable prostacyclin analogue beraprost is mediated through cAMP-responsive element in vascular endothelial cells: close link between PGI2 signal and NO pathways. Circ. Res. 2003, 93:523-530.
44. Pullamsetti S., Krick S., Yilmaz H., Ghofrani H.A., Schudt C., Weissmann N., Fuchs B., Seeger W., Grimminger F., Schermuly R.T. Inhaled tolafentrine reverses pulmonary vascular remodeling via inhibition of smooth muscle cell migration. Respir. Res. 2005, 6:28.
45. Rodat L., Savineau J.P., Marthan R., Guibert C. Effect of chronic hypoxia on voltage-independent calcium influx activated by 5-HT in rat intrapulmonary arteries. Pfluegers Arch. 2007, 454:41-51.
46. 2+ channels. Am. J. Physiol. Lung Cell. Mol. Physiol. 2007, 292:L685-L698.
47. 2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol. Rev. 2003, 83:1325-1358.
48. Taraseviciene-Stewart L., Scerbavicius R., Choe K.H., Cool C., Wood K., Tuder R.M., Burns N., Kasper M., Voelkel N.F. Simvastatin causes endothelial cell apoptosis and attenuates severe pulmonary hypertension. Am. J. Physiol. Lung Cell. Mol. Physiol. 2006, 291:L668-L676.
49. Wang J., Shimoda L.A., Sylvester J.T. Capacitative calcium entry and TRPC channel proteins are expressed in rat distal pulmonary arterial smooth muscle. Am. Physiol. Lung. Cell. Mol. Physiol. 2004, 286:L848-L858.
50. Zhu C.B., Hewlett W.A., Francis S.H., Corbin J.D., Blakely R.D. Stimulation of serotonin transport by the cyclic GMP phosphodiesterase-5 inhibitor sildenafil. Eur. J. Pharmacol. 2004, 504:1-6.