A protease inhibitor against acute stress-induced visceral hypersensitivity and paracellular permeability in rats.
Abstract
In the present study, we investigated the effects of camostat mesilate (CM), a synthetic protease inhibitor, on visceral sensitivity and paracellular permeability induced by the acute restraint stress. We also explored the possible mechanisms underlying these effects. The acute restraint stress was induced by wrapping the fore shoulders, upper forelimbs and thoracic trunk of Sprague-Dawley rats for 2h. Either CM (30, 100 and 300mg/kg) or saline was intragastrically administrated to the rats 30min before the acute restraint stress. Visceral perception was quantified as visceral motor response with an electromyography in a subset of rats. Paracellular permeability was determined in another subset of rats. We found that the visceral sensitivity and paracellular permeability were significantly reduced in the CM-treated rats. Moreover, the fecal protease activity was decreased in the CM-treated rats. The ZO-1 protein expression was markedly reduced by the stress treatment, but this decrease was suppressed by CM administration. Our data indicated that CM could efficiently inhibit visceral sensitivity and paracellular permeability induced by the acute restraint stress in rats. Therefore, CM might be an effective drug for the treatment of irritable bowel syndrome.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Psychological stress adversely affects intestinal barrier function, resulting in increased intestinal permeability.
“It is well-known that intestinal barrier function can be adversely affected by acute or chronic psychological stress, resulting in increased intestinal permeability [2], [3], [4], [5], [6]”
From CRF induces intestinal epithelial barrier injury via the release of mast cell proteases and TNF-α (2012) · cites this paper as [3]
Cites
Fanning, A. S., Jameson, B. J., Jesaitis, L. A., & Anderson, J. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.45.29745 · Cited by 1,432 · see citing works
Spiller, R. C., Jenkins, D., Thornley, J. P., Hebden, J. M., Wright, T., Skinner, M., & Neal, K. R. (2000) · Gut · doi:10.1136/gut.47.6.804 · Cited by 1,155 · see citing works
Itoh, M., Furuse, M., Morita, K., Kubota, K., Saitou, M., & Tsukita, S. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.6.1351 · Cited by 1,151 · see citing works
Psychosocial Factors in the Irritable Bowel Syndrome
Drossman, D. A., McKee, D. C., Sandler, R. S., Mitchell, C. M., Cramer, E. M., Lowman, B. C., & Burger, A. L. (1988) · Gastroenterology · doi:10.1016/s0016-5085(88)80017-9 · Cited by 757 · see citing works
Role for protease activity in visceral pain in irritable bowel syndrome
Cenac, N., Andrews, C. N., Holzhausen, M., Chapman, K., Cottrell, G., Andrade-Gordon, P., Steinhoff, M., Barbara, G., Beck, P., Bunnett, N. W., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29255 · Cited by 591 · see citing works
Rome III: New standard for functional gastrointestinal disorders.
Drossman, D. A., & Dumitrascu, D. L. (2006) · PubMed · Cited by 584 · see citing works
Piche, T., Barbara, G., Aubert, P., Bruley des Varannes, S., Dainese, R., Nano, J. L., Cremon, C., Stanghellini, V, De Giorgio, R., Galmiche, J. P., et al. (2009) · Gut · doi:10.1136/gut.2007.140806 · Cited by 540 · see citing works
IV. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells
Nusrat, A., Turner, J. R., & Madara, J. (2000) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2000.279.5.g851 · Cited by 499 · see citing works
Symptoms of Psychologic Distress Associated With Irritable Bowel Syndrome
Whitehead, W. E., Bosmajian, L., Zonderman, A. B., Costa Jr., P. T., & Schuster, M. M. (1988) · Gastroenterology · doi:10.1016/s0016-5085(88)80018-0 · Cited by 480 · see citing works
Abnormal Intestinal Permeability in Subgroups of Diarrhea-Predominant Irritable Bowel Syndromes
Dunlop, S. P., Hebden, J., Campbell, E., Naesdal, J., Olbe, L., Perkins, A. C., & Spiller, R. C. (2006) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2006.00672.x · Cited by 476 · see citing works
Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome
Zhou, Q., Zhang, B., & Verne, N. G. (2009) · Pain · doi:10.1016/j.pain.2009.06.017 · Cited by 373 · see citing works
Gecse, K., Róka, R., Ferrier, L., Leveque, M., Eutamene, H., Cartier, C., Ait-Belgnaoui, A., Rosztóczy, A., Izbéki, F., Fioramonti, J., et al. (2008) · Gut · doi:10.1136/gut.2007.140210 · Cited by 314 · see citing works
Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat
Santos, J., Yang, P.-C., Söderholm, J. D., Benjamin, M., & Perdue, M. H. (2001) · Gut · doi:10.1136/gut.48.5.630 · Cited by 313 · see citing works
Marshall, J. K., Thabane, M., Garg, A. X., Clark, W., Meddings, J., Collins, S. M., & for the WEL Investigators (2004) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2004.02284.x · Cited by 292 · see citing works
Stress‐induced visceral hypersensitivity to rectal distension in rats: role of CRF and mast cells
Gué, M., Rio-Lacheze, C. D., Eutamène, H., Théodorou, V., Fioramonti, J., & Bueno, L. P. (1997) · Neurogastroenterology & Motility · doi:10.1046/j.1365-2982.1997.d01-63.x · Cited by 282 · see citing works
Acute stressors stimulate ion secretion and increase epithelial permeability in rat intestine
Saunders, P. R., Kosecka, U., McKay, D. M., & Perdue, M. H. (1994) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1994.267.5.g794 · Cited by 215 · see citing works
Ferrier, L., Mazelin, L., Cénac, N., Desreumaux, P., Janin, A., Émilie, D., Colombel, J., Villar, R. G., Fioramonti, J., & Bueno, L. P. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)01057-6 · Cited by 197 · see citing works
Synthetic inhibitors of trypsin, plasmin, kallikrein, thrombin, , and C1 esterase
Tamura, Y., Hirado, M., Okamura, K., Minato, Y., & Fujii, S. (1977) · Biochimica et Biophysica Acta (BBA) - Enzymology · doi:10.1016/0005-2744(77)90097-3 · Cited by 178 · see citing works
Ait-Belgnaoui, A., Bradesi, S., Fioramonti, J., Theodorou, V., & Bueno, L. (2005) · Pain · doi:10.1016/j.pain.2004.10.002 · Cited by 171 · see citing works
CLINICAL RELEVANCE OF PROTEINASE ACTIVATED RECEPTORS (PARS) IN THE GUT
Vergnolle, N. (2005) · Gut · doi:10.1136/gut.2004.048876 · Cited by 166 · see citing works
Savas, L. S., White, D. L., Wieman, M. S., Daci, K., Fitzgerald, S. J., SMITH, S. L., Tan, G., Graham, D. P., Cully, J. A., & EL‐SERAG, H. B. (2008) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2008.03847.x · Cited by 90 · see citing works
Kerckhoffs, A. P. M., Linde, J. J. M. T., Akkermans, L. M. A., & Samsom, M. (2008) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2008.01100.x · Cited by 82 · see citing works
Crane, J. W., French, K. R., & Buller, K. M. (2005) · Stress · doi:10.1080/10253890500333817 · Cited by 64 · see citing works
Role of Intestinal Permeability in Monitoring Mucosal Barrier Function
Sun, Z., Wang, X., & Andersson, R. (1998) · Digestive Surgery · doi:10.1159/000018651 · Cited by 58 · see citing works
Saito‐Nakaya, K., Hasegawa, R., Nagura, Y., Ito, H., & Fukudo, S. (2008) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2008.01151.x · Cited by 49 · see citing works
Protease-activated receptors: protease signaling in the gastrointestinal tract
Amadesi, S., & Bunnett, N. W. (2004) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2004.08.004 · Cited by 49 · see citing works
Demaude, J., Levêque, M., Chaumaz, G., Eutamène, H., Fioramonti, J., Bueno, L. P., & Ferrier, L. (2009) · Life Sciences · doi:10.1016/j.lfs.2009.03.016 · Cited by 33 · see citing works
The proteinase inhibitor camostat mesilate suppresses pancreatic pain in rodents
Ishikura, H., Nishimura, S., Matsunami, M., Tsujiuchi, T., Ishiki, T., Sekiguchi, F., Naruse, M., Nakatani, T., Kamanaka, Y., & Kawabata, A. (2007) · Life Sciences · doi:10.1016/j.lfs.2007.02.044 · Cited by 32 · see citing works
Treatment of Ulcerative Colitis with Camostat Mesilate, A Serine Protease Inhibitor.
Senda, S., Fujiyama, Y., Bamba, T., & Hosoda, S. (1993) · Internal Medicine · doi:10.2169/internalmedicine.32.350 · Cited by 27 · see citing works
Kono, K., Takahashi, A., Sugai, H., Umekawa, T., Yano, T., Kamiyasu, K., Teramatsu, M., & Fujii, H. (2005) · The American Journal of Surgery · doi:10.1016/j.amjsurg.2005.05.044 · Cited by 25 · see citing works
Rey, E., Alonso, M. O. G., Moreno-Ortega, M., Almansa, C., Álvarez-Sánchez, Á., & Díaz‐Rubio, M. (2008) · Digestive Diseases and Sciences · doi:10.1007/s10620-008-0352-5 · Cited by 20 · see citing works
Róka, R., Wittmann, T., & Bueno, L. P. (2008) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2008.01155.x · Cited by 14 · see citing works
Ikeda, T., Murakami, K., Hayakawa, Y., Fujii, H., Ohkoshi, M., & SAIKI, I. (1998) · PubMed · Cited by 11 · see citing works
Quigley, E. M. M. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.06.024 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
CRF induces intestinal epithelial barrier injury via the release of mast cell proteases and TNF-α
Overman, E. L., Rivier, J. E., & Moeser, A. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039935 · Cited by 207 · see citing works
Regulation of intestinal permeability: The role of proteases
Spaendonk, H. V., Ceuleers, H., Witters, L., Patteet, E., Joossens, J., Augustyns, K., Lambeir, A., Meester, I. D., Man, J. G. D., & Winter, B. Y. D. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i12.2106 · Cited by 191 · see citing works
Leigh, S., Uhlig, F., Wilmes, L., Sánchez-Díaz, P., Gheorghe, C. E., Goodson, M. S., Kelley‐Loughnane, N., Hyland, N. P., Cryan, J. F., & Clarke, G. A. (2023) · The Journal of Physiology · doi:10.1113/jp281951 · Cited by 193 · see citing works
Ruan, Z., Liu, S., Zhou, Y., Mi, S., Liu, G., Wu, X., Kang, Y., Assaad, H., Deng, Z., Hou, Y., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097815 · Cited by 122 · see citing works
Kanwal, S., Joseph, T. P., Owusu, L., Ren, X., Li, M., & Xin, Y. (2018) · Nutrients · doi:10.3390/nu10081003 · Cited by 109 · see citing works
Anti-nociceptive effect of Faecalibacterium prausnitzii in non-inflammatory IBS-like models
Miquel, S., Martín, R., Lashermes, A., Gillet, M., Meleine, M., Gelot, A., Eschalier, A., Ardid, D., Bermúdez-Humarán, L. G., Sokol, H., et al. (2016) · Scientific Reports · doi:10.1038/srep19399 · Cited by 105 · see citing works
Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin
Meerveld, B. G., & Johnson, A. C. (2017) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2017.00086 · Cited by 97 · see citing works
Zhao, Y., Qin, G., Sun, Z., Che, D., Bao, N., & Zhang, X. (2011) · International Journal of Molecular Sciences · doi:10.3390/ijms12128502 · Cited by 94 · see citing works
Meerveld, B. G., Prusator, D. K., & Johnson, A. C. (2015) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00463.2014 · Cited by 76 · see citing works
Ceuleers, H., Spaendonk, H. V., Hanning, N., Heirbaut, J., Lambeir, A., Joossens, J., Augustyns, K., Man, J. G. D., Meester, I. D., & Winter, B. Y. D. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i47.10275 · Cited by 63 · see citing works
Ceuleers, H., Hanning, N., Heirbaut, J., Van Remoortel, S., Joossens, J., Van Der Veken, P., Francque, S. M., De bruyn, M., Lambeir, A., De Man, J. G., et al. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14396 · Cited by 49 · see citing works
Siddiqui, N. Z., Rehman, A. U., Yousuf, W., Khan, A. I., Farooqui, N. A., Zang, S., Xin, Y., & Wang, L. (2022) · Gut Pathogens · doi:10.1186/s13099-022-00512-1 · Cited by 47 · see citing works
Luo, R., Yang, Q., Huang, X., Yan, Z., Gao, X., Wang, W., Xie, K., Wang, P., & Gun, S. (2020) · Gene · doi:10.1016/j.gene.2020.144999 · Cited by 42 · see citing works
Wu, H., Gao, X., Jiang, Z., Duan, Z., Wang, S., He, B., Zhang, Z., & Xie, H. (2012) · Toxicology · doi:10.1016/j.tox.2012.11.020 · Cited by 41 · see citing works
β-Conglycinin Reduces the Tight Junction Occludin and ZO-1 Expression in IPEC-J2
Zhao, Y., Qin, G., Han, R., Wang, J., Zhang, X., & Liu, D. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15021915 · Cited by 38 · see citing works
Self-citationGarabadu, D., Shah, A., Singh, S. K., & Krishnamurthy, S. (2014) · Pharmaceutical Biology · doi:10.3109/13880209.2014.950674 · Cited by 33 · see citing works
Zhang, M., Zhao, J., Deng, J., Duan, Z., Zhu, C., & Fan, D. (2019) · Food & Function · doi:10.1039/c9fo00242a · Cited by 32 · see citing works
Self-citationCritical Evaluation of Animal Models of Gastrointestinal Disorders
Johnson, A. C., & Meerveld, B. G. (2017) · Handbook of experimental pharmacology · doi:10.1007/164_2016_120 · Cited by 29 · see citing works
Soybean allergen glycinin induced the destruction of the mechanical barrier function in IPEC-J2
Zhao, Y., Liu, D., Han, R., Zhang, X., Zhang, S., & Qin, G. (2015) · Food and Agricultural Immunology · doi:10.1080/09540105.2014.998638 · Cited by 28 · see citing works
Role of Stress on Driving the Intestinal Paracellular Permeability
Molotla‐Torres, D. E., Guzmán‐Mejía, F., Godínez‐Victoria, M., & Drago-Serrano, M. E. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45110581 · Cited by 26 · see citing works
Chen, B., Yang, X., Zhan, M., Chen, Y., Xu, J., Xiao, J., Xiao, H., & Song, M. (2023) · Food & Function · doi:10.1039/d3fo02998k · Cited by 22 · see citing works
Torres-Maravilla, E., Holowacz, S., Delannoy, J., Lenoir, L., Jacouton, E., Gervason, S., Meynier, M., Boucard, A.-S., Carvalho, F. A., Barbut, F., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-21746-8 · Cited by 20 · see citing works
Hanning, N., bruyn, M. D., Ceuleers, H., Boogaerts, T., Berg, M., Smet, A., Schepper, H. U. D., Joossens, J., van Nuijs, A. L. N., Man, J. G. D., et al. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13060811 · Cited by 18 · see citing works
Khan, U., Mubariz, M., Khlidj, Y., Nasir, M. M., Ramadan, S., Saeed, F. O., Muhammad, A., & Abuelazm, M. T. (2024) · BMC Infectious Diseases · doi:10.1186/s12879-024-09468-w · Cited by 16 · see citing works
Inhibition of Serine Proteases as a Novel Therapeutic Strategy for Abdominal Pain in IBS
Decraecker, L., Boeckxstaens, G. E., & Denadai‐Souza, A. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.880422 · Cited by 15 · see citing works
Wen, Y., Ullah, H., Ma, R., Farooqui, N. A., Li, J., Alioui, Y., & Qiu, J. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e39390 · Cited by 9 · see citing works
Orock, A. M., Yuan, T., & Meerveld, B. G. (2021) · Frontiers in Pain Research · doi:10.3389/fpain.2020.609292 · Cited by 10 · see citing works
Ceuleers, H., Hanning, N., bruyn, M. D., Man, J. G. D., Schepper, H. U. D., Li, Q., Liu, L., Abrams, S., Smet, A., Joossens, J., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.765744 · Cited by 8 · see citing works
Chen, J., Zhang, T., Liu, Y., Dong, X., & Liu, J. (2024) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00060.2024 · Cited by 6 · see citing works
Ullah, H., Ali, M., Ma, R., Alioui, Y., Ali, S., Ilyas, M., Rahman, M. U., Farooqui, N. A., Siddiqui, N. Z., Xin, Y., et al. (2024) · Journal of Functional Foods · doi:10.1016/j.jff.2024.106350 · Cited by 5 · see citing works
Zhang, B., Yang, W., Zhang, H., Meng, Q., Bi, C., & Shan, A. (2019) · Journal of Animal Physiology and Animal Nutrition · doi:10.1111/jpn.13194 · Cited by 4 · see citing works
Kanazawa, M., Miyamoto, K., Kano, M., Inooka, K., Oka, K., Takahashi, M., Mano, N., & Fukudo, S. (2024) · Digestion · doi:10.1159/000542758 · Cited by 2 · see citing works
Lee, J., Cho, C. S., Jeong, H. C., Kim, J. H., Jo, D. H., & Kim, G. B. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117555
Khan, U., Mubariz, M., Khlidj, Y., Nasir, M. M., Ramadan, S., Saeed, F., Muhammad, A., & Abuelazm, M. (2024) · Figshare · doi:10.6084/m9.figshare.26339885
Siddiqui, N. Z., Rehman, A. U., Yousuf, W., khan, A. I., Farooqui, N. A., Zang, S., Xin, Y., & Wang, L. (2022) · Figshare · doi:10.6084/m9.figshare.21152942
- Authors
- Zhao, J., Wang, J., Dong, L., Shi, H., Wang, Z., Ding, H., Shi, H., & Lu, X.
- Affiliations
- Second Affiliated Hospital of Xi'an Jiaotong University (CN)
- Corresponding author
- Wang, Jinhai
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 654
- Issue
- 3
- Pages
- 289-294
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2135833528
- Cited by
- 35
- References
- 34
- Citations by year
- 2025: 1 · 2024: 6 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 3 · 2012: 2
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- camostat mesilate, protease inhibitors, visceral hypersensitivity, acute restraint stress, visceral pain, paracellular permeability, ZO-1, tight junctions, irritable bowel syndrome
- MeSH terms
- Animals, Colon, Female, Gene Expression Regulation, Membrane Proteins, Permeability, Phosphoproteins, Protease Inhibitors, Rectum, Restraint, Physical, Stress, Psychological, Rats, Sprague-Dawley, Rats, Zonula Occludens-1 Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
