Protease-activated receptors: How proteases signal to cells to cause inflammation and pain

Seminars in Thrombosis and Hemostasis

Volumn 32, Issue SUPPL. 1, 2006, Pages 39-48

  Bunnett, Nigel W ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Cell surface proteases; Inflammation; Neurogenic inflammation; Nociception; Protease activated receptors

Indexed keywords

BLOOD CLOTTING FACTOR; CALCITONIN GENE RELATED PEPTIDE; G PROTEIN COUPLED RECEPTOR; GRANZYME A; MYELOBLASTIN; NEUROPEPTIDE; PROTEINASE; PROTEINASE ACTIVATED RECEPTOR; PROTEINASE ACTIVATED RECEPTOR 2; PROTEINASE ACTIVATED RECEPTOR BLOCKER; PROTEINASE INHIBITOR; RECEPTOR BLOCKING AGENT; SUBSTANCE P; TRYPSIN; TRYPTASE; UNCLASSIFIED DRUG;

CELL INFILTRATION; CELL MEMBRANE PERMEABILITY; DISEASE MODEL; ENZYME ACTIVITY; ENZYME RELEASE; EPITHELIUM; EXTRAVASATION; GRANULOCYTE; HEMOSTASIS; HYPEREMIA; INFLAMMATION; INFLAMMATORY CELL; NERVE CELL; NEUROGENIC INFLAMMATION; NOCICEPTION; NONHUMAN; PAIN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN SECRETION; REVIEW; SENSORY NERVE; SPINAL CORD DORSAL HORN; TISSUE REPAIR;

ANIMALS; HUMANS; INFLAMMATION; PAIN; PEPTIDE HYDROLASES; RECEPTORS, PROTEINASE-ACTIVATED; SIGNAL TRANSDUCTION;

EID: 33646483932     PISSN: 00946176     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2006-939553     Document Type: Review

References (84)

1. Macfarlane SR, Scatter MJ, Kanke T, Hunter GD, Plevin R. Proteinase-activated receptors. Pharmacol Rev 2001;53:245-282
2. Coughlin SR. Protease-activated receptors in vascular biology. Thromb Haemost 2001;86:298-307
3. Vergnolle N, Wallace JL, Bunnett NW, Hollenberg MD. Protease-activated receptors in inflammation, neuronal signaling and pain. Trends Pharmacol Sci 2001;22:146-152
4. Ossovskaya VS, Bunnett NW. Protease-activated receptors: contribution to physiology and disease. Physiol Rev 2004; 84:579-621
5. Kanke T, Ishiwata H, Kabeya M, et al. Binding of a highly potent protease-activated receptor-2 (PAR2) activating peptide, [3H]2-furoyl-LIGRL-NH2, to human PAR2. Br J Pharmacol 2005;145:255-263
6. Andrade-Gordon P, Maryanoff BE, Derian CK, et al. Design, synthesis, and biological characterization of a peptide-mimetic antagonist for a tethered-ligand receptor. Proc Natl Acad Sci USA 1999;96:12257-12262
7. Vu TK, Wheaton VI, Hung DT, Charo I, Coughlin SR. Domains specifying thrombin-receptor interaction. Nature 1991;353:674-677
8. Ishihara H, Connolly AJ, Zeng D, et al. Protease-activated receptor 3 is a second thrombin receptor in humans. Nature 1997;386:502-506
9. Xu WF, Andersen H, Whitmore TE, et al. Cloning and characterization of human protease-activated receptor 4. Proc Natl Acad Sci USA 1998;95:6642-6646
10. Kahn ML, Zheng YW, Huang W, et al. A dual thrombin receptor system for platelet activation. Nature 1998;394:690-694
11. Nakanishi-Matsui M, Zheng YW, Sulciner DJ, et al. PAR3 is a cofactor for PAR4 activation by thrombin. Nature 2000; 404:609-613
12. Camerer E, Huang W, Coughlin SR. Tissue factor- and factor X-dependent activation of protease-activated receptor 2 by factor VIIa. Proc Natl Acad Sci USA 2000;97:5255-5260
13. Riewald M, Ruf W. Mechanistic coupling of protease signaling and initiation of coagulation by tissue factor. Proc Natl Acad Sci USA 2001;98:7742-7747
14. Camerer E, Kataoka H, Kahn M, Lease K, Coughlin SR. Genetic evidence that protease-activated receptors mediate factor Xa signaling in endothelial cells. J Biol Chem 2002; 277:16081-16087
15. Riewald M, Petrovan RJ, Donner A, Mueller BM, Ruf W. Activation of endothelial cell protease activated receptor 1 by the protein C pathway. Science 2002;296:1880-1882
16. Griffin JH, Zlokovic B, Fernandez JA. Activated protein C: potential therapy for severe sepsis, thrombosis, and stroke. Semin Hematol 2002;39:197-205
17. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699-709
18. Cheng T, Liu D, Griffin JH, et al. Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective. Nat Med 2003;9:338-342
19. Guo H, Liu D, Gelbard H, et al. Activated protein C prevents neuronal apoptosis via protease activated receptors 1 and 3. Neuron 2004;41:563-572
20. Brueckmann M, Horn S, Lang S, et al. Recombinant human activated protein C upregulates cyclooxygenase-2 expression in endothelial cells via binding to endothelial cell protein C receptor and activation of protease-activated receptor-1. Thromb Haemost 2005;93:743-750
21. Wiegand U, Corbach S, Minn A, Kang J, Muller-Hill B. Cloning of the cDNA encoding human brain trypsinogen and characterization of its product. Gene 1993;136:167-175
22. Cottrell GS, Amadesi S, Grady EF, Bunnett NW. Trypsin IV, a novel agonist of protease-activated receptors 2 and 4. J Biol Chem 2004;279:13532-13539
23. Kong W, McConalogue K, Khitin LM, et al. Luminal trypsin may regulate enterocytes through proteinase-activated receptor 2. Proc Natl Acad Sci USA 1997;94:8884-8889
24. Katona G, Berglund GI, Hajdu J, Graf L, Szilagyi L. Crystal structure reveals basis for the inhibitor resistance of human brain trypsin. J Mol Biol 2002;315:1209-1218
25. Molino M, Barnathan ES, Numerof R, et al. Interactions of mast cell tryptase with thrombin receptors and PAR-2. J Biol Chem 1997;272:4043-4049
26. Corvera CU, Dery O, McConalogue K, et al. Mast cell tryptase regulates rat colonic myocytes through proteinase-activated receptor 2. J Clin Invest 1997;100:1383-1393
27. Reed DE, Barajas-Lopez C, Cottrell G, et al. Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea-pig submucosal neurons. J Physiol 2003; 547:531-542
28. Huang C, De Sanctis GT, O'Brien PJ, et al. Evaluation of the substrate specificity of human mast cell tryptase beta I and demonstration of its importance in bacterial infections of the lung. J Biol Chem 2001;276:26276-26284
29. Compton SJ, Renaux B, Wijesuriya SJ, Hollenberg MD. Glycosylation and the activation of proteinase-activated receptor 2 (PAR(2)) by human mast cell tryptase. Br J Pharmacol 2001;134:705-718
30. Sambrano GR, Huang W, Faruqi T, et al. Cathepsin G activates protease-activated receptor-4 in human platelets. J Biol Chem 2000;275:6819-6823
31. Uehara A, Sugawara S, Muramoto K, Takada H. Activation of human oral epithelial cells by neutrophil proteinase 3 through protease-activated receptor-2. J Immunol 2002;169:4594-4603
32. Nystedt S, Ramakrishnan V, Sundelin J. The proteinase-activated receptor 2 is induced by inflammatory mediators in human endothelial cells. Comparison with the thrombin receptor. J Biol Chem 1996;271:14910-14915
33. Cicala C, Pinto A, Bucci M, et al. Protease-activated receptor-2 involvement in hypotension in normal and endotoxemic rats in vivo. Circulation 1999;99:2590-2597
34. Hamilton JR, Cocks TM. Heterogeneous mechanisms of endothelium-dependent relaxation for thrombin and peptide activators of protease-activated receptor-1 in porcine isolated coronary artery. Br J Pharmacol 2000;130:181-188
35. Hamilton JR, Moffatt JD, Frauman AG, Cocks TM. Protease-activated receptor (PAR)1 but not PAR2 or PAR4 mediates endothelium-dependent relaxation to thrombin and trypsin in human pulmonary arteries. J Cardiovasc Pharmacol 2001;38:108-119
36. Hamilton JR, Moffatt JD, Tatoulis J, Cocks TM. Enzymatic activation of endothelial protease-activated receptors is dependent on artery diameter in human and porcine isolated coronary arteries. Br J Pharmacol 2002;136:492-501
37. Roy SS, Saifeddine M, Loutzenhiser R, Triggle CR, Hollenberg MD. Dual endothelium-dependent vascular activities of proteinase-activated receptor-2-activating peptides: evidence for receptor heterogeneity. Br J Pharmacol 1998;123:1434-1440
38. Robin J, Kharbanda R, Mclean P, Campbell R, Vallance P. Protease-activated receptor 2-mediated vasodilatation in humans in vivo: role of nitric oxide and prostanoids. Circulation 2003;107:954-959
39. Vergnolle N, Hollenberg MD, Wallace JL. Pro- and anti-inflammatory actions of thrombin: a distinct role for proteinase-activated receptor-1 (PAR1). Br J Pharmacol 1999;126:1262-1268
40. de Garavilla L, Vergnolle N, Young SH, et al. Agonists of proteinase-activated receptor 1 induce plasma extravasation by a neurogenic mechanism. Br J Pharmacol 2001;133:975-987
41. Steinhoff M, Vergnolle N, Young SH, et al. Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat Med 2000;6:151-158
42. Vergnolle N, Derian CK, D'Andrea MR, Steinhoff M, Andrade-Gordon P. Characterization of thrombin-induced leukocyte rolling and adherence: a potential proinflammatory role for proteinase-activated receptor-4. J Immunol 2002;169:1467-1473
43. Vergnolle N. Proteinase-activated receptor-2-activating peptides induce leukocyte rolling, adhesion, and extravasation in vivo. J Immunol 1999;163:5064-5069
44. Zhu WJ, Yamanaka H, Obata K, et al. Expression of mRNA for four subtypes of the proteinase-activated receptor in rat dorsal root ganglia. Brain Res 2005;1041:205-211
45. Cenac N, Coelho AM, Nguyen C, et al. Induction of intestinal inflammation in mouse by activation of proteinase-activated receptor-2. Am J Pathol 2002;161:1903-1915
46. Cenac N, Garcia-Villar R, Ferrier L, et al. Proteinase-activated receptor-2-induced colonic inflammation in mice: possible involvement of afferent neurons, nitric oxide, and paracellular permeability. J Immunol 2003;170:4296-4300
47. Green BT, Bunnett NW, Kulkarni-Narla A, Steinhoff M, Brown DR. Intestinal type 2 proteinase-activated receptors: expression in opioid-sensitive secretomotor neural circuits that mediate epithelial ion transport. J Pharmacol Exp Ther 2000;295:410-416
48. Buresi MC, Vergnolle N, Sharkey KA, et al. Activation of proteinase-activated receptor-1 inhibits neurally evoked chloride secretion in the mouse colon in vitro. Am J Physiol Gastrointest Liver Physiol 2005;288:G337-G345
49. Gao C, Liu S, Hu HZ, et al. Serine proteases excite myenteric neurons through protease-activated receptors in guinea pig small intestine. Gastroenterology 2002;123:1554-1564
50. Chin AC, Vergnolle N, MacNaughton WK, et al. Proteinase-activated receptor 1 activation induces epithelial apoptosis and increases intestinal permeability. Proc Natl Acad Sci USA 2003;100:11104-11109
51. Cenac N, Chin AC, Garcia-Villar R, et al. PAR2 activation alters colonic paracellular permeability in mice via IFN-gamma-dependent and -independent pathways. J Physiol 2004;558:913-925
52. Jacob C, Yang PC, Darmoul D, et al. Mast cell tryptase controls paracellular permeability of the intestine: Role of protease-activated receptor 2 and beta-arrestins. J Biol Chem 2005;280:31936-31948
53. Vergnolle N, Cellars L, Mencarelli A, et al. A role for proteinase-activated receptor-1 in inflammatory bowel diseases. J Clin Invest 2004;114:1444-1456
54. Hansen KK, Sherman PM, Cellars L, et al. A major role for proteolytic activity and proteinase-activated receptor-2 in the pathogenesis of infectious colitis. Proc Natl Acad Sci USA 2005;102:8363-8368
55. Fiorucci S, Mencarelli A, Palazzetti B, et al. Proteinase-activated receptor 2 is an anti-inflammatory signal for colonic lamina propria lymphocytes in a mouse model of colitis. Proc Natl Acad Sci USA 2001;98:13936-13941
56. Kawabata A, Kinoshita M, Nishikawa H, et al. The protease-activated receptor-2 agonist induces gastric mucus secretion and mucosal cytoprotection. J Clin Invest 2001;107:1443-1450
57. Nguyen TD, Moody MW, Steinhoff M, et al. Trypsin activates pancreatic duct epithelial cell ion channels through proteinase-activated receptor-2. J Clin Invest 1999;103:261-269
58. Namkung W, Han W, Luo X, et al. Protease-activated receptor 2 exerts local protection and mediates some systemic complications in acute pancreatitis. Gastroenterology 2004; 126:1844-1859
59. Sharma A, Tao X, Gopal A, et al. Protection against acute pancreatitis by activation of protease-activated receptor-2. Am J Physiol Gastrointest Liver Physiol 2005;288:G388-G395
60. Cocks TM, Fong B, Chow JM, et al. A protective role for protease-activated receptors in the airways. Nature 1999; 398:156-160
61. Schmidlin F, Amadesi S, Dabbagh K, et al. Protease-activated receptor 2 mediates eosinophil infiltration and hyperreactivity in allergic inflammation of the airway. J Immunol 2002; 169:5315-5321
62. Takizawa T, Tamiya M, Hara T, et al. Abrogation of bronchial eosinophilic inflammation and attenuated eotaxin content in protease-activated receptor 2-deficient mice. J Pharmacol Sci 2005;98:99-102
63. Ebeling C, Forsythe P, Ng J, et al. Proteinase-activated receptor 2 activation in the airways enhances antigen-mediated airway inflammation and airway hyperresponsiveness through different pathways. J Allergy Clin Immunol 2005;115:623-630
64. De Campo BA, Henry PJ. Stimulation of protease-activated receptor-2 inhibits airway eosinophilia, hyperresponsiveness and bronchoconstriction in a murine model of allergic inflammation. Br J Pharmacol 2005;144:1100-1108
65. Howell DC, Johns RH, Lasky JA, et al. Absence of proteinase-activated receptor-1 signaling affords protection from bleomycin-induced lung inflammation and fibrosis. Am J Pathol 2005;166:1353-1365
66. Ferrell WR, Lockhart JC, Kelso EB, et al. Essential role for proteinase-activated receptor-2 in arthritis. J Clin Invest 2003;111:35-41
67. Yang YH, Hall P, Little CB, et al. Reduction of arthritis severity in protease-activated receptor-deficient mice. Arthritis Rheum 2005;52:1325-1332
68. Marty I, Peclat V, Kirdaite G, et al. Amelioration of collagen-induced arthritis by thrombin inhibition. J Clin Invest 2001;107:631-640
69. Vergnolle N, Bunnett NW, Sharkey KA, et al. Proteinase-activated receptor-2 and hyperalgesia: a novel pain pathway. Nat Med 2001;7:821-826.
70. Hoogerwerf WA, Zou L, Shenoy M, et al. The proteinase-activated receptor 2 is involved in nociception. J Neurosci 2001;21:9036-9042
71. Kawabata A, Kawao N, Kuroda R, et al. Peripheral PAR-2 triggers thermal hyperalgesia and nociceptive responses in rats. Neuroreport 2001;12:715-719
72. Hoogerwerf WA, Shenoy M, Winston JH, et al. Trypsin mediates nociception via the proteinase-activated receptor 2: a potentially novel role in pancreatic pain. Gastroenterology 2004;127:883-891
73. Coelho AM, Vergnolle N, Guiard B, Fioramonti J, Bueno L. Proteinases and proteinase-activated receptor 2: a possible role to promote visceral hyperalgesia in rats. Gastroenterology 2002;122:1035-1047
74. Caterina MJ, Schumacher MA, Tominaga M, et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997;389:816-824
75. Amadesi S, Nie J, Vergnolle N, et al. Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia. J Neurosci 2004;24:4300-4312
76. Dai Y, Moriyama T, Higashi T, et al. Proteinase-activated receptor 2-mediated potentiation of transient receptor potential vanilloid subfamily 1 activity reveals a mechanism for proteinase-induced inflammatory pain. J Neurosci 2004; 24:4293-4299
77. Kawabata A, Kinoshita M, Kuroda R, Kakehi K. Capsazepine partially inhibits neurally mediated gastric mucus secretion following activation of protease-activated receptor 2. Clin Exp Pharmacol Physiol 2002;29:360-361
78. Barbara G, Stanghellini V, De Giorgio R, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology 2004;126:693-702
79. Connolly AJ, Ishihara H, Kahn ML, Farese RV Jr, Coughlin SR. Role of the thrombin receptor in development and evidence for a second receptor. Nature 1996;381:516-519
80. Cunningham MA, Rondeau E, Chen X, et al. Protease-activated receptor 1 mediates thrombin-dependent, cell-mediated renal inflammation in crescentic glomerulonephritis. J Exp Med 2000;191:455-462
81. Junge CE, Sugawara T, Mannaioni G, et al. The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebral ischemia. Proc Natl Acad Sci USA 2003;100:13019-13024
82. Lindner JR, Kahn ML, Coughlin SR, et al. Delayed onset of inflammation in protease-activated receptor-2-deficient mice. J Immunol 2000;165:6504-6510
83. Weiss EJ, Hamilton JR, Lease KE, Coughlin SR. Protection against thrombosis in mice lacking PAR3. Blood 2002; 100:3240-3244
84. Hamilton JR, Cornelissen I, Coughlin SR. Impaired hemostasis and protection against thrombosis in protease-activated receptor 4-deficient mice is due to lack of thrombin signaling in platelets. J Thromb Haemost 2004;2:1429-1435