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Open Access 01-12-2007 | Research article

Mandatory role of proteinase-activated receptor 1 in experimental bladder inflammation

Authors: Ricardo Saban, Michael R D'Andrea, Patricia Andrade-Gordon, Claudia K Derian, Igor Dozmorov, Michael A Ihnat, Robert E Hurst, Carole A Davis, Cindy Simpson, Marcia R Saban

Published in: BMC Physiology | Issue 1/2007

Abstract

Background

In general, inflammation plays a role in most bladder pathologies and represents a defense reaction to injury that often times is two edged. In particular, bladder neurogenic inflammation involves the participation of mast cells and sensory nerves. Increased mast cell numbers and tryptase release represent one of the prevalent etiologic theories for interstitial cystitis and other urinary bladder inflammatory conditions. The activity of mast cell-derived tryptase as well as thrombin is significantly increased during inflammation. Those enzymes activate specific G-protein coupled proteinase-activated receptors (PAR)s.

Four PARs have been cloned so far, and not only are all four receptors highly expressed in different cell types of the mouse urinary bladder, but their expression is altered during experimental bladder inflammation. We hypothesize that PARs may link mast cell-derived proteases to bladder inflammation and, therefore, play a fundamental role in the pathogenesis of cystitis.

Results

Here, we demonstrate that in addition to the mouse urinary bladder, all four PA receptors are also expressed in the J82 human urothelial cell line. Intravesical administration of PAR-activating peptides in mice leads to an inflammatory reaction characterized by edema and granulocyte infiltration. Moreover, the inflammatory response to intravesical instillation of known pro-inflammatory stimuli such as E. coli lipopolysaccharide (LPS), substance P, and antigen was strongly attenuated by PAR1-, and to a lesser extent, by PAR2-deficiency.

Conclusion

Our results reveal an overriding participation of PAR1 in bladder inflammation, provide a working model for the involvement of downstream signaling, and evoke testable hypotheses regarding the role of PARs in bladder inflammation. It remains to be determined whether or not mechanisms targeting PAR1 gene silencing or PAR1 blockade will ameliorate the clinical manifestations of cystitis.

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Hilmy M, Campbell R, Bartlett JM, McNicol AM, Underwood MA, McMillan DC: The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic infiltration and COX-2 expression and survival in patients with transitional cell carcinoma of the urinary bladder. Br J Cancer. 2006, 95 (9): 1234-1238. 10.1038/sj.bjc.6603415.PubMedCentralPubMed

Cai T, Nesi G, Boddi V, Mazzoli S, Dal Canto M, Bartoletti R: Prognostic role of the tumor-associated tissue inflammatory reaction in transitional bladder cell carcinoma. Oncol Rep. 2006, 16 (2): 329-334.PubMed

Gu J, Grossman HB, Dinney CP, Wu X: The pharmacogenetic impact of inflammatory genes on bladder cancer recurrence. Pharmacogenomics. 2005, 6 (6): 575-584. 10.2217/14622416.6.6.575.PubMed

Offersen BV, Knap MM, Marcussen N, Horsman MR, Hamilton-Dutoit S, Overgaard J: Intense inflammation in bladder carcinoma is associated with angiogenesis and indicates good prognosis. Br J Cancer. 2002, 87 (12): 1422-1430. 10.1038/sj.bjc.6600615.PubMedCentralPubMed

Theoharides TC, Cochrane DE: Critical role of mast cells in inflammatory diseases and the effect of acute stress. J Neuroimmunol. 2004, 146 (1–2): 1-12. 10.1016/j.jneuroim.2003.10.041.PubMed

Boucher W, el-Mansoury M, Pang X, Sant GR, Theoharides TC: Elevated mast cell tryptase in the urine of patients with interstitial cystitis. Br J Urol. 1995, 76 (1): 94-100.PubMed

Yamada T, Murayama T, Mita H, Akiyama K: Subtypes of bladder mast cells in interstitial cystitis. Int J Urol. 2000, 7 (8): 292-297. 10.1046/j.1442-2042.2000.00197.x.PubMed

Tomaszewski JE, Landis JR, Russack V, Williams TM, Wang LP, Hardy C, Brensinger C, Matthews YL, Abele ST, Kusek JW: Biopsy features are associated with primary symptoms in interstitial cystitis: results from the interstitial cystitis database study. Urology. 2001, 57 (6 Suppl 1): 67-81. 10.1016/S0090-4295(01)01166-9.PubMed

D'Andrea MR, Saban MR, Gerard NP, Wershil BK, Saban R: Lack of neurokinin-1 receptor expression affects tissue mast cell numbers but not their spatial relationship with nerves. Am J Physiol Regul Integr Comp Physiol. 2005, 288 (2): R491-500.PubMed

10.

Saban R, Gerard NP, Saban MR, Nguyen NB, DeBoer DJ, Wershil BK: Mast cells mediate substance P-induced bladder inflammation through an NK(1) receptor-independent mechanism. Am J Physiol Renal Physiol. 2002, 283 (4): F616-629.PubMed

11.

Saban R, Saban MR, Nguyen NB, Hammond TG, Wershil BK: Mast cell regulation of inflammation and gene expression during antigen-induced bladder inflammation in mice. Physiol Genomics. 2001, 7 (1): 35-43.PubMed

12.

Ustinova EE, Gutkin DW, Pezzone MA: Sensitization of Pelvic Nerve Afferents and Mast Cell Infiltration in the Urinary Bladder Following Chronic Colonic Irritation is Mediated by Neuropeptides. Am J Physiol Renal Physiol. 2006

13.

Cao J, Boucher W, Kempuraj D, Donelan JM, Theoharides TC: Acute stress and intravesical corticotropin-releasing hormone induces mast cell dependent vascular endothelial growth factor release from mouse bladder explants. J Urol. 2006, 176 (3): 1208-1213. 10.1016/j.juro.2006.04.026.PubMed

14.

Bouchelouche K, Bouchelouche P: Cysteinyl leukotriene D4 increases human detrusor muscle responsiveness to histamine. J Urol. 2006, 176 (1): 361-366. 10.1016/S0022-5347(06)00513-1.PubMed

15.

Okragly AJ, Niles AL, Saban R, Schmidt D, Hoffman RL, Warner TF, Moon TD, Uehling DT, Haak-Frendscho M: Elevated tryptase, nerve growth factor, neurotrophin-3 and glial cell line-derived neurotrophic factor levels in the urine of interstitial cystitis and bladder cancer patients. J Urol. 1999, 161 (2): 438-441. 10.1016/S0022-5347(01)61915-3. discussion 441–432.PubMed

16.

Vergnolle N, Cellars L, Mencarelli A, Rizzo G, Swaminathan S, Beck P, Steinhoff M, Andrade-Gordon P, Bunnett NW, Hollenberg MD: A role for proteinase-activated receptor-1 in inflammatory bowel diseases. Journal of Clinical Investigation. 2004, 114 (10): 1444-10.1172/JCI200421689.PubMedCentralPubMed

17.

Cenac N, Garcia-Villar R, Ferrier L, Larauche M, Vergnolle N, Bunnett NW, Coelho AM, Fioramonti J, Bueno L: Proteinase-activated receptor-2-induced colonic inflammation in mice: possible involvement of afferent neurons, nitric oxide, and paracellular permeability. J Immunol. 2003, 170 (8): 4296-4300.PubMed

18.

Schmidlin F, Amadesi S, Dabbagh K, Lewis DE, Knott P, Bunnett NW, Gater PR, Geppetti P, Bertrand C, Stevens ME: Protease-activated receptor 2 mediates eosinophil infiltration and hyperreactivity in allergic inflammation of the airway. J Immunol. 2002, 169 (9): 5315-5321.PubMed

19.

Steinhoff M, Vergnolle N, Young SH, Tognetto M, Amadesi S, Ennes HS, Trevisani M, Hollenberg MD, Wallace JL, Caughey GH: Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat Med. 2000, 6 (2): 151-158. 10.1038/72247.PubMed

20.

Ossovskaya VS, Bunnett NW: Protease-activated receptors: contribution to physiology and disease. Physiol Rev. 2004, 84 (2): 579-621. 10.1152/physrev.00028.2003.PubMed

21.

Amadesi S, Nie J, Vergnolle N, Cottrell GS, Grady EF, Trevisani M, Manni C, Geppetti P, McRoberts JA, Ennes H: Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia. J Neurosci. 2004, 24 (18): 4300-4312. 10.1523/JNEUROSCI.5679-03.2004.PubMed

22.

Reed DE, Barajas-Lopez C, Cottrell G, Velazquez-Rocha S, Dery O, Grady EF, Bunnett NW, Vanner S: Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea pig submucosal neurons. J Physiol. 2003, 10-1113/jphysiol.2002.032011.

23.

Vergnolle N, Wallace JL, Bunnett NW, Hollenberg MD: Protease-activated receptors in inflammation, neuronal signaling and pain. Trends Pharmacol Sci. 2001, 22 (3): 146-152. 10.1016/S0165-6147(00)01634-5.PubMed

24.

Vergnolle N, Bunnett NW, Sharkey KA, Brussee V, Compton SJ, Grady EF, Cirino G, Gerard N, Basbaum AI, Andrade-Gordon P: Proteinase-activated receptor-2 and hyperalgesia: A novel pain pathway. Nat Med. 2001, 7 (7): 821-826. 10.1038/89945.PubMed

25.

Hollenberg D, Compton S: International Union of Pharmacology. XXVIII. Proteinase-Activated Receptors. Pharmacol Reviews. 2002, 54: 203-217. 10.1124/pr.54.2.203.

26.

Vergnolle N: Review article: proteinase-activated receptors – novel signals for gastrointestinal pathophysiology. Aliment Pharmacol Ther. 2000, 14 (3): 257-266. 10.1046/j.1365-2036.2000.00690.x.PubMed

27.

D'Andrea MR, Saban MR, Nguyen NB, Andrade-Gordon P, Saban R: Expression of protease-activated receptor-1, -2, -3, and -4 in control and experimentally inflamed mouse bladder. Am J Pathol. 2003, 162 (3): 907-923.PubMedCentralPubMed

28.

Sakai T, Noguchi M, Kisiel W: Tumor cells augment the factor Xa-catalyzed conversion of prothrombin to thrombin. Haemostasis. 1990, 20 (3): 125-135.PubMed

29.

Lummen G, Virchow S, Rumenapp U, Schmidt M, Wieland T, Otto T, Rubben H, Jakobs KH: Identification of G protein-coupled receptors potently stimulating migration of human transitional-cell carcinoma cells. Naunyn Schmiedebergs Arch Pharmacol. 1997, 356 (6): 769-776. 10.1007/PL00005117.PubMed

30.

McHowat J, Creer MH, Rickard A: Stimulation of protease activated receptors on RT4 cells mediates arachidonic acid release via Ca2+ independent phospholipase A2. J Urol. 2001, 165 (6 Pt 1): 2063-2067.PubMed

31.

Dattilio A, Vizzard MA: Up-regulation of protease activated receptors in bladder after cyclophosphamide induced cystitis and colocalization with capsaicin receptor (VR1) in bladder nerve fibers. J Urol. 2005, 173 (2): 635-639. 10.1097/01.ju.0000143191.55468.1d.PubMed

32.

Saban MR, Nguyen NB, Hammond TG, Saban R: Gene expression profiling of mouse bladder inflammatory responses to LPS, substance P, and antigen-stimulation. Am J Pathol. 2002, 160 (6): 2095-2110.PubMedCentralPubMed

33.

Saito K, Muto T, Tomimori Y, Maruoka H, Tanaka T, Fukuda Y: Human chymase stimulates Ca2+ signaling in human polymorphonuclear cells. Immunology letters. 2003, 89 (2–3): 161-165. 10.1016/S0165-2478(03)00129-9.PubMed

34.

Schechter NM, Brass LF, Lavker RM, Jensen PJ: Reaction of mast cell proteases tryptase and chymase with protease activated receptors (PARs) on keratinocytes and fibroblasts. J Cell Physiol. 1998, 176 (2): 365-373. 10.1002/(SICI)1097-4652(199808)176:2<365::AID-JCP15>3.0.CO;2-2.PubMed

35.

Ui H, Andoh T, Lee JB, Nojima H, Kuraishi Y: Potent pruritogenic action of tryptase mediated by PAR-2 receptor and its involvement in anti-pruritic effect of nafamostat mesilate in mice. Eur J Pharmacol. 2006, 530 (1–2): 172-178. 10.1016/j.ejphar.2005.11.021.PubMed

36.

Kelso EB, Lockhart JC, Hembrough T, Dunning L, Plevin R, Hollenberg MD, Sommerhoff CP, McLean JS, Ferrell WR: Therapeutic promise of proteinase-activated receptor-2 antagonism in joint inflammation. J Pharmacol Exp Ther. 2006, 316 (3): 1017-1024. 10.1124/jpet.105.093807.PubMed

37.

Noorbakhsh F, Tsutsui S, Vergnolle N, Boven LA, Shariat N, Vodjgani M, Warren KG, Andrade-Gordon P, Hollenberg MD, Power C: Proteinase-activated receptor 2 modulates neuroinflammation in experimental autoimmune encephalomyelitis and multiple sclerosis. J Exp Med %R 101084/jem20052148. 2006, 203 (2): 425-435. 10.1084/jem.20052148.

38.

Darrow AL, Fung-Leung WP, Ye RD, Santulli RJ, Cheung WM, Derian CK, Burns CL, Damiano BP, Zhou L, Keenan CM: Biological consequences of thrombin receptor deficiency in mice. Thromb Haemost. 1996, 76 (6): 860-866.PubMed

39.

Junge CE, Sugawara T, Mannaioni G, Alagarsamy S, Conn PJ, Brat DJ, Chan PH, Traynelis SF: The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebral ischemia. Proc Natl Acad Sci USA. 2003, 100 (22): 13019-13024. 10.1073/pnas.2235594100.PubMedCentralPubMed

40.

Lindner JR, Kahn ML, Coughlin SR, Sambrano GR, Schauble E, Bernstein D, Foy D, Hafezi-Moghadam A, Ley K: Delayed onset of inflammation in protease-activated receptor-2-deficient mice. J Immunol. 2000, 165 (11): 6504-6510.PubMed

41.

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 (18): 16081-16087. 10.1074/jbc.M108555200.PubMed

42.

Kawagoe J, Takizawa T, Matsumoto J, Tamiya M, Meek SE, Smith AJ, Hunter GD, Plevin R, Saito N, Kanke T: Effect of protease-activated receptor-2 deficiency on allergic dermatitis in the mouse ear. Japanese journal of pharmacology. 2002, 88 (1): 77-84. 10.1254/jjp.88.77.PubMed

43.

Su X, Camerer E, Hamilton JR, Coughlin SR, Matthay MA: Protease-activated receptor-2 activation induces acute lung inflammation by neuropeptide-dependent mechanisms. J Immunol. 2005, 175 (4): 2598-2605.PubMed

44.

Kawabata A, Kawao N, Kitano T, Matsunami M, Satoh R, Ishiki T, Masuko T, Kanke T, Saito N: Colonic hyperalgesia triggered by proteinase-activated receptor-2 in mice: involvement of endogenous bradykinin. Neurosci Lett. 2006, 402 (1–2): 167-172. 10.1016/j.neulet.2006.03.074.PubMed

45.

Nakahara T, Kubota Y, Saito M, Sakamoto K, Ishii K: Protease-activated receptor-2-mediated contraction of urinary bladder is enhanced in cyclophosphamide-treated rats. Naunyn Schmiedebergs Arch Pharmacol. 2004, 369 (2): 212-219. 10.1007/s00210-003-0847-8.PubMed

46.

de Garavilla L, Vergnolle N, Young SH, Ennes H, Steinhoff M, Ossovskaya VS, D'Andrea MR, Mayer EA, Wallace JL, Hollenberg MD: Agonists of proteinase-activated receptor 1 induce plasma extravasation by a neurogenic mechanism. Br J Pharmacol. 2001, 133 (7): 975-987. 10.1038/sj.bjp.0704152.PubMed

47.

Saban R, Saban MR, Nguyen NB, Lu B, Gerard C, Gerard NP, Hammond TG: Neurokinin-1 (NK-1) receptor is required in antigen-induced cystitis. Am J Pathol. 2000, 156: 775-780.PubMedCentralPubMed

48.

Saban MR, Saban R, Hammond TG, Haak-Frendscho M, Steinberg H, Tengowski MW, Bjorling DE: LPS-sensory peptide communication in experimental cystitis. Am J Physiol Renal Physiol. 2002, 282 (2): F202-210.PubMed

49.

Abraham D, Oster H, Huber M, Leitges M: The expression pattern of three mast cell specific proteases during mouse development. Mol Immunol. 2007, 44 (5): 732-740. 10.1016/j.molimm.2006.04.019.PubMed

50.

Kim DK, Lee YM: Requirement of c-jun transcription factor on the mouse mast cell protease-6 expression in the mast cells. Arch Biochem Biophys. 2004, 431 (1): 71-78. 10.1016/j.abb.2004.07.027.PubMed

51.

Wong GW, Yasuda S, Morokawa N, Li L, Stevens RL: Mouse chromosome 17A3.3 contains thirteen genes that encode functional tryptic-like serine proteases with distinct tissue and cell expression patterns. J Biol Chem. 2003

52.

Funaba M, Ikeda T, Murakami M, Ogawa K, Nishino Y, Tsuchida K, Sugino H, Abe M: Transcriptional regulation of mouse mast cell protease-7 by TGF-beta. Biochimica et biophysica acta. 2006, 1759 (3–4): 166-170.PubMed

53.

Oikonomopoulou K, Hansen KK, Saifeddine M, Tea I, Blaber M, Blaber SI, Scarisbrick I, Andrade-Gordon P, Cottrell GS, Bunnett NW: Proteinase-activated receptors, targets for kallikrein signaling. J Biol Chem. 2006, 281 (43): 32095-32112. 10.1074/jbc.M513138200.PubMed

54.

de Groat WC: Integrative control of the lower urinary tract: preclinical perspective. Br J Pharmacol. 2006, 147 (Suppl 2): S25-40. 10.1038/sj.bjp.0706604.PubMedCentralPubMed

55.

Macfarlane SR, Seatter MJ, Kanke T, Hunter GD, Plevin R: Proteinase-activated receptors. Pharmacological reviews. 2001, 53 (2): 245-282.PubMed

56.

Ludeman MJ, Zheng YW, Ishii K, Coughlin SR: Regulated shedding of PAR1 N-terminal exodomain from endothelial cells. J Biol Chem. 2004, 279 (18): 18592-18599. 10.1074/jbc.M310836200.PubMed

57.

Nakahara T, Kubota Y, Mitani A, Maruko T, Sakamoto K, Ishii K: Protease-activated receptor-2-mediated contraction in the rat urinary bladder: the role of urinary bladder mucosa. Naunyn Schmiedebergs Arch Pharmacol. 2003, 367 (2): 211-213. 10.1007/s00210-002-0687-y.PubMed

58.

Kubota Y, Nakahara T, Mitani A, Maruko T, Saito M, Sakamoto K, Ishii K: Possible involvement of Ca2+-independent phospholipase A2 in protease-activated receptor-2-mediated contraction of rat urinary bladder. Naunyn Schmiedebergs Arch Pharmacol. 2003, 367 (6): 588-591. 10.1007/s00210-003-0753-0.PubMed

59.

Portell C, Rickard A, Vinson S, McHowat J: Prostacyclin production in tryptase and thrombin stimulated human bladder endothelial cells: effect of pretreatment with phospholipase A2 and cyclooxygenase inhibitors. J Urol. 2006, 176 (4 Pt 1): 1661-1665. 10.1016/j.juro.2006.06.041.PubMed

60.

Rickard A, Portell C, Kell PJ, Vinson SM, McHowat J: Protease-activated receptor stimulation activates a Ca2+-independent phospholipase A2 in bladder microvascular endothelial cells. American journal of physiology. 2005, 288 (4): F714-721.PubMed

61.

Rickard A, McHowat J: Phospholipid metabolite production in human urothelial cells after protease-activated receptor cleavage. American journal of physiology. 2002, 283 (5): F944-951.PubMed

62.

Major CD, Santulli RJ, Derian CK, Andrade-Gordon P: Extracellular mediators in atherosclerosis and thrombosis: lessons from thrombin receptor knockout mice. Arterioscler Thromb Vasc Biol. 2003, 23 (6): 931-939. 10.1161/01.ATV.0000070100.47907.26.PubMed

63.

Coughlin SR: Protease-activated receptors in hemostasis, thrombosis and vascular biology. J Thromb Haemost. 2005, 3 (8): 1800-1814. 10.1111/j.1538-7836.2005.01377.x.PubMed

64.

Tang H, Low B, Rutherford SA, Hao Q: Thrombin induces endocytosis of endoglin and type-II TGF-beta receptor and down-regulation of TGF-beta signaling in endothelial cells. Blood. 2005, 105 (5): 1977-1985. 10.1182/blood-2004-08-3308.PubMed

65.

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 (1): 108-119. 10.1097/00005344-200107000-00012.PubMed

66.

Dery O, Corvera CU, Steinhoff M, Bunnett NW: Proteinase-activated receptors: novel mechanisms of signaling by serine proteases. Am J Physiol. 1998, 274 (6 Pt 1): C1429-1452.PubMed

67.

Kong W, McConalogue K, Khitin LM, Hollenberg MD, Payan DG, Bohm SK, Bunnett NW: Luminal trypsin may regulate enterocytes through proteinase-activated receptor 2. Proc Natl Acad Sci USA. 1997, 94 (16): 8884-8889. 10.1073/pnas.94.16.8884.PubMedCentralPubMed

68.

Cocks TM, Fong B, Chow JM, Anderson GP, Frauman AG, Goldie RG, Henry PJ, Carr MJ, Hamilton JR, Moffatt JD: A protective role for protease-activated receptors in the airways. Nature. 1999, 398 (6723): 156-160. 10.1038/18223.PubMed

69.

Noorbakhsh F, Tsutsui S, Vergnolle N, Boven LA, Shariat N, Vodjgani M, Warren KG, Andrade-Gordon P, Hollenberg MD, Power C: Proteinase-activated receptor 2 modulates neuroinflammation in experimental autoimmune encephalomyelitis and multiple sclerosis. J Exp Med. 2006, 203 (2): 425-435. 10.1084/jem.20052148.PubMedCentralPubMed

70.

Gatti R, Andre E, Amadesi S, Dinh TQ, Fischer A, Bunnett NW, Harrison S, Geppetti P, Trevisani M: Protease-activated receptor-2 activation exaggerates TRPV1-mediated cough in guinea pigs. J Appl Physiol. 2006, 101 (2): 506-511. 10.1152/japplphysiol.01558.2005.PubMed

71.

Luo W, Wang Y, Hanck T, Stricker R, Reiser G: Jab1, a novel protease-activated receptor-2 (PAR-2)-interacting protein, is involved in PAR-2-induced activation of activator protein-1. J Biol Chem. 2006, 281 (12): 7927-7936. 10.1074/jbc.M510784200.PubMed

72.

[http://frodo.wi.mit.edu/cgi-bin/primer3/primer3_www.cgi]

73.

Asokananthan N, Graham PT, Fink J, Knight DA, Bakker AJ, McWilliam AS, Thompson PJ, Stewart GA: Activation of protease-activated receptor (PAR)-1, PAR-2, and PAR-4 stimulates IL-6, IL-8, and prostaglandin E2 release from human respiratory epithelial cells. J Immunol. 2002, 168 (7): 3577-3585.PubMed

74.

[http://rsb.info.nih.gov/ij/]

75.

Damiano BP, Cheung WM, Santulli RJ, Fung-Leung WP, Ngo K, Ye RD, Darrow AL, Derian CK, de Garavilla L, Andrade-Gordon P: Cardiovascular responses mediated by protease-activated receptor-2 (PAR-2) and thrombin receptor (PAR-1) are distinguished in mice deficient in PAR-2 or PAR-1. J Pharmacol Exp Ther. 1999, 288 (2): 671-678.PubMed

76.

Haak-Frendscho M, Saban R, Shields RL, Jardieu PM: Anti-immunoglobulin E antibody treatment blocks histamine release and tissue contraction in sensitized mice. Immunology. 1998, 94 (1): 115-121. 10.1046/j.1365-2567.1998.00478.x.PubMedCentralPubMed

77.

Dozmorov I, Saban MR, Gerard NP, Lu B, Nguyen NB, Centola M, Saban R: Neurokinin 1 receptors and neprilysin modulation of mouse bladder gene regulation. Physiol Genomics. 2003, 12 (3): 239-250.PubMed

78.

Saban MR, Nguyen NB, Hurst RE, Saban R: Gene expression profiling of inflammatory bladder disorders. Expert Rev Mol Diagn. 2003, 3 (2): 217-235. 10.1586/14737159.3.2.217.PubMed

79.

Faruqi TR, Weiss EJ, Shapiro MJ, Huang W, Coughlin SR: Structure-function analysis of protease-activated receptor 4 tethered ligand peptides. Determinants of specificity and utility in assays of receptor function. J Biol Chem. 2000, 275 (26): 19728-19734. 10.1074/jbc.M909960199.PubMed

Title: Mandatory role of proteinase-activated receptor 1 in experimental bladder inflammation
Authors: Ricardo Saban
Michael R D'Andrea
Patricia Andrade-Gordon
Claudia K Derian
Igor Dozmorov
Michael A Ihnat
Robert E Hurst
Carole A Davis
Cindy Simpson
Marcia R Saban
Publication date: 01-12-2007
Publisher: BioMed Central
Published in: BMC Physiology / Issue 1/2007
Electronic ISSN: 1472-6793
DOI: https://doi.org/10.1186/1472-6793-7-4

2024 ASCO Annual Meeting

Springer Medicine

Mandatory role of proteinase-activated receptor 1 in experimental bladder inflammation

Abstract

Background

Results

Conclusion

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Results

Conclusion

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