Julio-Septiembre 2015 63
ISSN 1317-987X
 
Buscar




Artículos
 



Hematología
La Trombina más allá de la coagulación (Revisión)

Referencias

1.- Lane DA, Philippou H, Huntington JA. Directing thrombin. Blood. 2005; 106: 2605-12

2.- Hirano K. The roles of proteinase-activated receptors in the vascular physiology and pathophysiology. Arterioscler Thromb Vasc Biol. 2007; 27: 27-36

3.- Carrillo-Esper R, de la Torre T, Rosales A. Complejo trombomodulina, proteína C, receptor endotelial de proteína C en sepsis. Revista de la Facultad de Medicina de la UNAM. 2013; 56: 14-25

4.- Spronk HM, Borissoff J, Ten Cate H. New Insights into Modulation of Thrombin Formation. . Curr Atheroscler Rep. 2013; 15: 1-9

5.- Naldini A, Aarde N, Pucci A, Bernini C, Carraro F. Inhibition of interleukin- 12 expression by a-thrombin in human peripheral blood mononuclear cells: a potential mechanism for modulating Th1/Th2 responses. Br J Pharmacol. 2003; 140: 980-6

6.- Naldini A, Bernini C, Pucci A, Carraro F. Thrombin-mediated IL-10 up-regulation involves protease activated receptor (PAR)-1 expression in human mononuclear leukocytes. J Leukoc Biol. 2005; 78: 736-44

7.- Coughlin SR. Thrombin signaling and protease-activated receptors. Nature. 2000; 407: 258-64.

8.- Patterson C, Stouffer G, Madamanchi N, Runge M. New tricks for old dogs nonthrombotic effects of thrombin in vessel wall biology. Circ Res. 2001; 88: 987-97.

9.- Spronk HM, de Jong AM, Crijns H, Schotten U, Van Gelder I, Ten Cate H. Pleiotropic effects of factor Xa and thrombin: what to expect from novel anticoagulants. Cardiovascular Res. 2014; 101: 344-51

10.- Bode W, Turk D, Karshikov A. The refined 1.9-A X ray crystal structure of D-Phe-Pro-Argchloromethylketone- inhibited human alpha-thrombin: structure analysis, overall structure, electrostatic properties, detailed active-site geometry, and structure-function relationships. Protein Sci. 1992; 1: 426-71

11.- Le Bonniec BF, Guinto ER, MacGillivray RT, Stone SR, Esmon CT. The role of thrombin’s Tyr- Pro-Pro-Trp motif in the interaction with fibrinogen, thrombomodulin, protein C, antithrombin III, and the Kunitz inhibitors. J Biol Chem. 1993; 268: 19055-61

12.- Rezaie, AR. Reactivities of the S2 and S3 subsite residues of thrombin with the native and heparin induced conformers of antithrombin. Protein Sci. 1998; 7: 349-57

13.- Orcutt SJ, Krishnaswamy S. Binding of substrate in two conformations to human prothrombinase drives consecutive cleavage at two sites in prothrombin. J Biol Chem. 2004; 279:54927-36.

14.- Wu Q, Picard V, Aiach M, Sadler JE. Activation-induced exposure of the thrombin anion-binding exosite. Interactions of recombinant mutant prothrombins with thrombomodulin and a thrombin exosite specific antibody. J Biol Chem. 1994; 269: 3725-30

15.- Chen R, Doolittle R. γ-γ cross-linking sites human and bovine fibrin. Biochemistry. 1971; 10: 4487-91

16.- Hongbao M, Young J, Shen C. Thrombin. J Nat Sci. 2008; 6: 90-3

17.- Broze G. Thrombin-dependent inhibition of fibrinolysis. Curr Opin Hematol. 1996; 3: 390-4

18.- Van Tilburg N, Rosendaal F, Bertina R. Thrombin activatable fibrinolysis inhibitor and the risk for deep vein thrombosis. Blood. 2000; 95:2855-9

19.- Esmon CT. The protein C pathway. Crit Care Med. 2000; 28:S44-8

20.- Sonne O. The specific binding of thrombin to human polymorphonuclear leucocytes. Scand J Clin Lab Invest. 1988; 48: 831-8

21.- Fenton J, Ofosu F, Brezniak D, Hassouna H. Thrombin and antithrombotics. Semin Thromb Hemost. 1998; 24:87-91.

22.- Hayes K, Leong L, Henriksen R, Bouchard B, Ouellette L, Church W, et al. alpha-thrombin - induced human platelet activation results solely from formation of a specific enzyme - substrate complex. J Biol Chem. 1994; 269: 28606-12

23.- Borissoff J, Spronk H, Heeneman S, ten Cate H. Is thrombin a key player in the ‘coagulation-atherogenesis’ maze? Cardiovasc Res. 2009; 82: 392-403

24.- Strande J, Phillips S. Thrombin increases inflammatory cytokine and angiogenic growth factor secretion in human adipose cells in vitro. Journal Inflamm (Lond). 2009; 6: 1-10

25.- García PS, Gulati A, Levy JH. The role of thrombin and protease-activated receptors in pain mechanisms. Thromb Haemost. 2010; 103: 1145-51

26.- Canto I, Soh UJ, Trejo J. Allosteric Modulation of Protease-activated Receptor Signaling. Med Chem. 2012; 12: 804-11

27.- Ku DD, Zaleski JK. Receptor mechanism of thrombin-induced endothelium-dependent and endothelium-independent coronary vascular effects in dogs. J Cardiovasc Pharmacol. 1993; 22: 609-16

28.- Derkach D, Ihara E, Hirano K, Nishimura J, Takahashi S, Kanaide H. Thrombin causes endothelium-dependent biphasic regulation of vascular tone in the porcine renal interlobar artery. Br J Pharmacol. 2000; 131: 1635-42

29.- Gudmundsdottir I, Lang N, Boon N, Ludlam C, Webb D, Fox K, et al. Role of the endothelium in the vascular effects of the thrombin receptor (protease-activated receptor type 1) in humans. J Am Coll Cardiol. 2008; 51:1749-56

30.- Watts VL, Motley ED. Role of protease-activated receptor-1 in endothelial nitric oxide synthase-Thr495 phosphorylation. Exp Biol Med (Maywood). 2009; 234: 132-9.

31.- Ming XF, Viswambharan H, Barandier C, Ruffieux J, Kaibuchi K, Rusconi S, et al. Rho GTPase/Rho kinase negatively regulates endothelial nitric oxide synthase phosphorylation through the inhibition of proteinkinase B/Akt in human endothelial cells. Mol Cell Biol. 2002; 22 (24): 8467-77

32.- Eto M, Barandier C, Rathgeb L, Kozai T, Joch H, Yang Z, et al. Thrombin suppresses endothelial nitric oxide synthase and upregulates endothelin-converting enzyme-1 expression by distinct pathways: role of Rho/ROCK and mitogen-activated protein kinase. Circ Res. 2001; 89: 583-90

33.- Ming XF, Barandier C, Viswambharan H, Kwak BR, Mach F, Mazzolai L, et al. Thrombin stimulates human endothelial arginase enzymatic activity via RhoA/ROCK pathway: implications for atherosclerotic endothelial dysfunction. Circulation. 2004; 110: 3708-14.

34.- Lewis C, Zhu W, Pavkov ML, Kinney CM, Dicorleto PE, Kashyap VS. Arginase blockade lessens endothelial dysfunction after thrombosis. J Vasc Surg. 2008; 48:441–6.

35.- Zhang C, Hein TW, Wang W, Miller MW, Fossum TW, McDonald MM, et al. Upregulation of vascular arginase in hypertension decreases nitric oxide-mediated dilation of coronary arterioles. Hypertension. 2004; 44: 935-43

36.- Tsopanoglou N, Maragoudakis M. Role of thrombin in angiogenesis and tumor progression. Semin Thromb Hemost. 2004; 30: 63-9.

37.- Rukoyatkina N, Begonja A, Geiger J, Eigenthaler M, Walter U, Gambaryan S. Phosphatidylserine surface expression and integrin alpha IIb beta 3 activity on thrombin/convulxin stimulated platelets/particles of different sizes. Br J Haematol. 2009; 144: 591-602

38.- Diebold I, Petry A, Djordjevic T, Belaiba R, Fineman J, Black S, et al. Reciprocal regulation of Rac1 and PAK-1 by HIF-1 alpha: a positive-feedback loop promoting pulmonary vascular remodeling. Antioxid Redox Signal. 2010; 13: 399-412

39.- Siller J, Schwameis M, Blann A, Mannhalter C, Jilma B. Thrombin as a multi-functional enzyme Focus on in vitro and in vivo effects. Thromb Haemost. 2011; 106: 1020-33

40.- Mohle R, Green D, Moore MA, Nachman RL, Rafii S. Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. Proc Natl Acad Sci. 1997; 94: 663-8

41.- Zucker S, Mirza H, Conner CE, Lorenz AF, Drews MH, Bahou WF, et al. Vascular endothelial growth factor induces tissue factor and matrix metalloproteinase production in endothelial cells: conversion of prothrombin to thrombin results in progelatinase A activation and cell proliferation. Int J Cancer. 1998; 75: 780-6

42.- Tsopanoglou N, Maragoudakis M. On the mechanism of thrombin induced angiogenesis: potentiation of vascular endothelial growth factor activity on endothelial cells by up-regulation of its receptors. J Biol Chem. 1999; 274: 23969-76

43.- Marin V, Farnarier C, Gres S, Kaplanski S, Su M, Dinarello C, et al. The p38 mitogen-activated protein kinase pathway plays a critical role in thrombin-induced endothelial chemokine production and leukocyte recruitment. Blood. 2001; 98: 667-73.

44.- Levi M, Keller TT, Van Gorp E, Ten Cate H. Infection and inflammation and the coagulation system. Cardiovasc Res. 2003; 60: 26-39.

45.- Levi M, Van der Poll T, Schultz M. Systemic versus localized coagulation activation contributing to organ failure in critically ill patients. Semin Immunopathol. 2012; 34: 167-79

46.- Florez, J. Farmacología Humana. 4ta. ed. España. Editorial Masson. 2003

47.- Goldsby R, Kindt T, Osborne B, Kuby J. Inmunología. 5ta. ed. México. McGraw-Hill Interamericana. 2004

48.- Parham, P. Inmunología. 2da. ed. Buenos Aires: Médica Panamericana. 2006.

49.- Cecilliani F, Giordano A, Spagnolo V. The systemic reaction during inflammation: The acute-phase proteins. Protein Pept lett. 2002; 9: 211-23

50.- Licastro F, Candore G, Lio D, Porcellini E, Colsonna-Romano G, Franceschi C, et al. Innate immunity and inflammation in ageing: a key for understanding age-related diseases. Immun Ageing. 2005; 2: 1-14.

51.- Vázquez, E, Navarro M, Salazar Y, Crespo G, Bruges G, Osorio C, et al. Systemic changes following carrageenan-induced paw inflammation in rats. Inflamm. Res. 2015; 64:333-42.

52.- Levi M, Van der Poll T, Schultz M. New insights into pathways that determine the link between infection and thrombosis. Neth J Med. 2012; 70: 114-20

53.- Rezaie, AR. The occupancy of endothelial protein C receptor by its ligand modulates the PAR-1 dependent signaling specificity of coagulation proteases. IUBMB Life. 2011; 63: 390-6

54.- Conway EM. Thrombomodulin and its role in inflammation. Semin Immunopathol. 2012; 34: 107-25.

55.- Esmon CT. Protein C anticoagulant system anti-inflammatory effects. Semin Immunopathol. 2012; 34: 127-32

56.- Borissoff J, Spronk H, ten Cate H. The hemostatic system as a modulator of atherosclerosis. N Engl J Med. 2011; 364:1746-60

57.- Szaba FM, Smiley ST. Roles for thrombin and fibrinogen in cytokine/chemokine production and macrophage adhesion in vivo. Blood. 2002; 99:1053-9.

58.- Tripathy D, Sanchez A, Yin X, Luo J, Martinez J, Grammas P. Thrombin,a mediator of cerebrovascular inflammation in AD and hypoxia. Front Aging Neurosci. 2013; 19: 1-9.

59.- Mihara M, Aihara K, Ikeda Y, Yoshida S, Kinouchi M, Kurahashi K, et al. Inhibition of thrombin action ameliorates insulin resistance in type 2 diabetic db/db mice. Endocrinology. 2010; 151: 513-9

60.- Tedgui A, Mallat Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev. 2006; 86: 515-81.

61.- Borissoff J, Heeneman H, Kilinc E, Kassak P, Van Oerle R, Winckers K, et al. Early atherosclerosis exhibits an enhanced procoagulant state. Circulation. 2010; 122: 821-30

62.- Borensztajn K, Spek CA. Blood coagulation factor Xa as an emerging drug target. Expert Opin Ther Targets. 2011; 15: 341-9

63.- Madamanchi NR, Li S, Patterson C, Runge MS. Thrombin regulates vascular smooth muscle cell growth and heat shock proteins via the JAK-STAT pathway. J Biol Chem. 2001; 276: 18915-24.

64.- Hamilton JR, Cornelissen I, Mountfordy JK, Coughlin SR. Atherosclerosis proceeds independently of thrombin-induced platelet activation in ApoE2/2 mice. Atherosclerosis. 2009; 205: 427-32

65.- Perlman H, Maillard L, Krasinski K, Walsh K. Evidence for the rapid onset of apoptosis in medial smooth muscle cells after balloon injury. Circulation. 1997; 95 (4): 981-7

66.- Baker A, Zaltsman A, George S, Newby A. Divergent effects of tissue inhibitor of metalloproteinase-1, -2, or -3 overexpression on rat vascular smooth muscle cell invasion, proliferation, and death in vitro: TIMP-3 promotes apoptosis. J Clin Invest. 1998; 101:1478-87

67.- Walsh K, Smith R, Kim H. Vascular cell apoptosis in remodeling, restenosis, and plaque rupture. Circ Res. 2000; 87:184-8

68.- Lutgens E, Lievens D, Beckers L, Donners M, Daemen M. CD40 and its ligand in atherosclerosis. Trends Cardiovasc Med. 2007; 17:118-23

69.- Von Hundelshausen P, Weber K, Huo Y, Proudfoot AE, Nelson PY, Ley K, et al. RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium. Circulation. 103: 1772-7.

70.- Piccardoni P, Evangelista V, Piccoli A, de Gaetano G, Walz A, Cerletti C. Thrombin-activated human platelets release two NAP-2 variants that stimulate polymorphonuclear leukocytes. Thromb Haemost. 1996; 76:780-5

71.- Pitsilos S, Hunt J, Mohler E, Prabhakar A, Poncz M, Dawicki J, et al. Platelet factor 4 localization in carotid atherosclerotic plaques: correlation with clinical parameters. Thromb Haemost. 2003; 90: 1112-20

72.- Lopez ML, Bruges G, Crespo G, Salazar V, Deglesne PA, Schneider H, et al. Thrombin selectively induces transcription of genes in human monocytes involved in inflammation and wound healing. Thromb. Haemost. 2014; 112: 992-1001.

73.- Koch M, Zernecke A. The Hemostatic System as a Regulator of Inflammation in Atherosclerosis. IUBMB Life. 2014; 66:735-44

74.- Amara U, Flierl M, Rittirsch D, Klos A, Chen H, Acker B, et al. Molecular intercommunication between the complement and coagulation systems. J Immunol. 2010; 185: 5628-36

75.- Speidl W, Kastl S, Huber K, Wojta J. Complement in atherosclerosis: friend or foe?. J. Thromb. Haemost. 2011; 9: 428-40.

76.- Bea F, Kreuzer J, Preusch M, Schaab S, Isermann B, Rosenfeld M, et al. Melagatran reduces advanced atherosclerotic lesion size and may promote plaque stability in apolipoprotein E-deficient mice. Arterioscler ThrombVasc Biol. 2006; 26: 2787-92.

77.- Lee IO, Kratz MT, Schirmer SH, Baumhakel M, Bohm M. The Effects of Direct Thrombin Inhibition with Dabigatran on Plaque Formation and Endothelial Function in Apolipoprotein E-Deficient Mice. J Pharmacol Exp Ther. 2012; 343: 253-7.

78.- Borissoff J, Otten J, Heeneman S, Leenders P, Van Oerle R, Soehnlein O, et al. Genetic and pharmacological modifications of thrombin formation in apolipoprotein E-deficient mice determine atherosclerosis severity and atherothrombosis onset in a neutrophil dependent manner. PLoS ONE. 2013; 8:e55784

79.- Brandes R, Viedt C, Nguyen K, Beer S, Kreuzer J, Busse R, et al. Thrombin-induced MCP-1 expression involves activation of the p22phox containing NADPH oxidase in human vascular smooth muscle cells. Thromb Haemost. 2001; 85:1104-10

80.- Gorlach A, Diebold I, Schini V, Berchner U, Roth U, Brandes R, et al. Thrombin activates the hypoxia-inducible factor-1 signaling pathway in vascular smooth muscle cells: Role of the p22 (phox)-containing NADPH oxidase. Circ Res. 2001; 89: 47-54

81.- Wachowicz B, Olas B, Zbikowska H, Buczynski A. Generation of reactive oxygen species in blood platelets. Platelets. 2002; 13:175

82.- Ushio M, Zafari A, Fukui T, Ishizaka N, Griendling K .p22phox is a critical component of the superoxide-generating NADH/NADPH oxidase system and regulates angiotensin II-induced hypertrophy in vascular smooth muscle cells. J Biol Chem. 271: 23317-21.

83.- Suh YA, Arnold RS, Lassegue B, Shi J, Xu X, Sorescu D, et al. Cell transformation by the superoxide-generating oxidase Mox1. Nature. 1999; 401: 79-82.

84.- Kanda Y, Mizuno K, Kuroki Y, Watanabe Y. Thrombin-induced p38mitogen-activated protein kinase activation is mediated by epidermal growth factor receptor transactivation pathway. Br J Pharmacol. 2001; 132:1657-64.

85.- Djordjevic T, Pogrebniak A, Belaiba R, Bonello S, Wotzlaw C, Acker H, et al. The expression of the NADPH oxidase subunit p22 phox is regulated by a redox-sensitive pathway in endothelial cells. Free Radic Biol Med. 2005; 38: 616-·30.

86.- Hawkins B, Solt L, Chowdhury I, Kazi A, Abid M, Aird W, et al. G protein-coupled receptor Ca2þ-linked mitochondrial reactive oxygen species are essential for endothelial/leukocyte adherence. Mol Cell Biol. 2007; 27: 7582-93.

87.- Rickles F, Patierno, Fernandez P. Tissue factor, thrombin, and cancer. Chest. 2003; 124: 58S-68S

88.- Kumar P, Shen Q, Pivetti CD, Lee ES, Wu MH, Yuan SY. Molecular mechanisms of endothelial hyperpermeability: implications in inflammation. Expert Rev Mol Med. 2009; 11: e19.

89.- Petaja J. Inflammation and coagulation. An overview. Thromb Res. 2011; 127: S34-7

90.- Franchini M, Montagnana M,Favaloro EJ,Lippi G. The bidirectional relationship of cancer and hemostasis and the potential role of anticoagulant therapy in moderating thrombosis and cancer spread. Semin Thromb Hemost. 2009; 35: 644-53

91.- Shirvaikar N, Marquez LA, Ratajczak MZ, Janowska A. Hyaluronic acid and thrombin upregulate MT1-MMP through PI3K and Rac-1 signaling and prime the homing-related responses of cord blood hematopoietic stem/progenitor cells. Stem Cells Dev. 2011; 20: 19-30.

92.- Tellez C, McCarty M, Ruiz M, Bar-Eli M. Loss of activator protein-2 a results in overexpression of protease-activated receptor-1 and correlates with the malignant phenotype of human melanoma. J Biol Chem. 2003; 278: 46632-42

93.- Darmoul D, Gratio V, Devaud H, Lehy T, Laburthe M. Aberrant expression and activation of the thrombin receptor protease-activated receptor-1 induce cell proliferation and motility in human colon cancer cells. Am. J. Pathol. 2003; 162: 1503-13

94.- Chay C, Cooper C, Gendernalik J, Dhanasekaran S, Chinnaiyan A, Rubin M, et al. A functional thrombin receptor (PAR1) is expressed on bone-derived prostate cancer cell lines. Urology. 2002; 60: 760-5

95.- Even-Ram S, Uziely B, Cohen P, Grisaru S, Maoz M, Ginzburg Y, et al. Thrombin receptor overexpression in malignant and physiological invasion processes. Nat. Med. 1998; 4: 909-14

96.- Yin Y, Salah Z, Grisaru S, Cohen I, Even-Ram S, Maoz M, et al. Human protease-activated receptor-1 expression in malignant epithelia: a role in invasiveness. Aterioscler Thromb Vasc Biol. 2003; 23: 940-4.

97.- Kahan C, Seuwen K , Meloche S, Pouyssegur J. Coordinate, biphasic activation of p44 mitogen-activated protein kinase and S6 kinase by growth factors in hamster fibroblasts. J Biol Chem. 1992; 267: 13369-75

98.- Trejo J, Connolly A, Coughlin S. The cloned thrombin receptor is necessary and sufficient for activation of mitogen-activated protein kinase and mitogenesis in mouse lung fibroblasts. Loss of responses in fibroblasts from receptor knockout mice. J Biol Chem. 1996; 271: 21536-41

99.- Bergmann S, Junker K, Henklein P, Hollenberg M, Settmacher U, Kaufmann R. PAR-type thrombin receptors in renal carcinoma cells: PAR1-mediated EGFR activation promotes cell migration. Oncol. Rep. 2006; 15: 889-93

100.- Even-Ram S, Maoz M, Pokroy E, Reich R, Katz B, Gutwein P, et al. Tumor cell invasion is promoted by protease-activated receptor-1 in cooperation with the alpha v beta 5 integrin. J Biol Chem. 2001; 276: 10952-62

101.- Guo H, Liu D, Gelbard H, Cheng T, Insalasco R, Fernandez J, et al. Activated protein C prevents neuronal apoptosis via protease activated receptors 1 and 3. Neuron. 2004; 41: 563-72

102.- Zania P, Kritikou S, Flordellis C, Maragoudakis M, Tsopanoglou N. Blockade of angiogenesis by small molecule antagonists to protease activated receptor-1: association with endothelial cell growth suppression and induction of apoptosis. J Pharmacol Exp Ther. 2006; 318: 246-54

103.- Arora P, Ricks T, Trejo J. 2007. Protease-activated receptor signalling, endocytic sorting and dysregulation in cancer. J Cell Sci. 2007; 120: 921-8

104.- Shi X, Gangadharan B, Brass LF, Ruf W, Mueller BM. Protease-activated receptor 1 (PAR1) and PAR2 contribute to tumor cell motility and metastasis. Mol Cancer Res. 2004; 2: 395-402

105.- O’Brien P, Prevost N, Molino M, Hollinger M, Woolkalis M, Woulfe D, et al. Thrombin responses in human endothelial cells. Contributions from receptors other than PAR1 include the transactivation of PAR2 by thrombin-cleaved PAR1. J Biol Chem. 2000; 275: 13502-9

106.- Belting M, Jasimuddin A, Wolfram R. Signaling of the Tissue Factor Coagulation Pathway in Angiogenesis and Cancer. Arterioscler Thromb Vasc Biol. 2005; 25: 1545-50

107.- Rothmeier AS, Ruf W. Protease-activated receptor 2 signaling in inflammation. Semin Immunopathol. 2012; 34:133-49

108.- Noorbakhsh F, Vergnolle N, Hollenberg M, Power C. Proteinase-activated receptors in the nervous system. Nat Neurosci. 2003; 4: 981-90

109.- Vergnolle N, Wallace J, Bunnett N, Hollenberg M. Protease-activated receptors in inflammation, neuronal signaling and pain. Trends Pharmacol Sci. 2001; 22: 146-52.

110.- Ossovskaya V, Bunnett N. Protease-activated receptors: contribution to physiology and disease. Physiol Rev. 2004; 84: 579-621.

111.- Saito T, Bunnett NW. Protease-activated receptors: regulation of neuronal function. Neuromolecular Med. 2005; 7: 79-99.

112.- Green B, Bunnett N, Kulkarni-Narla A, Steinhoff M, Brown D. Intestinal type 2 proteinase-activated receptors: expression in opioid-sensitive secretomotor neural circuits that mediate epithelial ion transport. J Pharmacol Exp Ther. 2000; 295: 410-6

113.- De Garavilla, Vergnolle N,Young SH,Ennes H,Steinhoff M,Ossovskaya VS, et al. Agonists of proteinase-activated receptor 1 induce plasma extravasation by a neurogenic mechanism. Br J Pharmacol. 2001; 133: 975-87

114.- Asfaha S, Brussee V, Chapman K, Zochodne D, Vergnolle N. Proteinase-activated receptors-1 agonists attenuate nociception in response to noxious stimuli. Br J Pharmacol. 2002; 135: 1101-6

115.- Gao C, Liu S, Hu H, Gao N, Kim G, Xia Y, et al. Serine proteases excite myenteric neurons through protease-activated receptors in guinea pig small intestine. Gastroenterology 2002; 123: 1554-64

116.- Kahn ML, Zheng YW, Huang C, Bigornia V, Zeng D, Moff S, et al. A dual thrombin receptor system for platelet activation. Nature. 1998; 394: 690-4

117.- Kataoka H, Hamilton J, McKemy D, Camerer E, Zheng Y, Cheng A, et al. Protease-activated receptors 1 and 4 mediate thrombin signaling in endothelial cells. Blood. 2003; 102: 3224-31

118.- Asfaha S, Cenac N, Houle S, Altier C, Papez MD, Nguyen C, et al. Protease-activated receptor-4: a novel mechanism of inflammatory pain modulation. Br J Pharmacol. 2007; 150: 176-85

119.- Narita M, Usui A, Narita M, Niikura K, Nozaki H, Khotib J, et al. Protease-activated receptor-1 and platelet-derived growth factor in spinal cord neurons are implicated in neuropathic pain after nerve injury. J Neurosci. 2005; 25: 10000-9


La Trombina más allá de la coagulación (Revisión)
Introducción
Efectos Pleiotrópicos de la Trombina
Trombina e Inflamación
Trombina y aterosclerosis
Trombina, proliferación celular y cáncer
Trombina, dolor nociceptivo y neuropático
Referencias

NOTA: Toda la información que se brinda en este artículo es de carácter investigativo y con fines académicos y de actualización para estudiantes y profesionales de la salud. En ningún caso es de carácter general ni sustituye el asesoramiento de un médico. Ante cualquier duda que pueda tener sobre su estado de salud, consulte con su médico o especialista.





Instituto de Medicina Tropical - Facultad de Medicina - Universidad Central de Venezuela.
Elaborado por el Centro de Análisis de Imágenes Biomédicas Computarizadas CAIBCO,
caibco@ucv.ve
Este portal ha sido desarrollado gracias al apoyo del Fonacit