Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome
Open accessAbstract
Background and aims: Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of α-helical CRH (αhCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients. Methods: Ten normal healthy subjects and 10 IBS patients, diagnosed according to the Rome II criteria, were studied. The tone of the descending colon and intraluminal pressure of the sigmoid colon were measured at baseline, during rectal electrical stimulation (ES), and at recovery after administration of saline. Visceral perception after colonic distension or rectal ES was evaluated as threshold values on an ordinate scale. The same measurements were repeated after administration of αhCRH (10 μg/kg). Results: ES induced significantly higher motility indices of the colon in IBS patients compared with controls. This response was significantly suppressed in IBS patients but not in controls after administration of αhCRH. Administration of αhCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. αhCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by ES in IBS patients. Plasma adrenocorticotropic hormone and serum cortisol levels were generally not suppressed by αhCRH. Conclusion: Peripheral administration of αhCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.
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AVP and CRH, by stimulating ACTH secretion, may affect the autonomic nervous system and colonic sensorimotor functions.
“AVP and CRH, by stimulating ACTH secretion, may affect the autonomic nervous system (38) and colonic sensorimotor functions (125, 152).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [152]
CRH may act directly on peripheral receptors of the ENS, independent of alterations in the HPA axis, to impact sensorimotor functions in patients with IBS.
“Additionally, CRH may act directly on peripheral receptors of the ENS, independent of alterations in the HPA axis, to impact sensorimotor functions in patients with IBS (152).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [152]
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Cites
Vale, W., Spiess, J., Rivier, C., & Rivier, J. (1981) · Science · doi:10.1126/science.6267699 · Cited by 3,965 · see citing works
Vale, W., Spiess, J., RIVIER, C. L., & Rivier, J. (1982) · Obstetrical & Gynecological Survey · doi:10.1097/00006254-198205000-00013 · Cited by 3,904 · see citing works
Functional bowel disorders and functional abdominal pain
Thompson, W. G., Longstreth, G. F., Drossman, D. A., Heaton, K. W., Irvine, E. J., & Müller-Lissner, S. A. (1999) · Gut · doi:10.1136/gut.45.2008.ii43 · Cited by 2,440 · see citing works
Dunn, A. J., & Berridge, C. W. (1990) · Brain Research Reviews · doi:10.1016/0165-0173(90)90012-d · Cited by 1,352 · see citing works
Physiology and pharmacology of corticotropin-releasing factor.
Owens, M. J., & Nemeroff, C. B. (1991) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06673-6 · Cited by 1,147 · see citing works
Tolerance for Rectosigmoid Distention in Irritable Bowel Syndrome
Whitehead, W. E., Holtkötter, B., Enck, P., Hoelzl, R., Holmes, K. D., Anthony, J. C., Shabsin, H. S., & Schuster, M. M. (1990) · Gastroenterology · doi:10.1016/0016-5085(90)90332-u · Cited by 592 · see citing works
Lovenberg, T. W., Chalmers, D. T., Liu, C., & Souza, E. B. D. (1995) · Endocrinology · doi:10.1210/endo.136.9.7544278 · Cited by 457 · see citing works
The functional gastrointestinal disorders
Olden, K. W. (1997) · General Hospital Psychiatry · doi:10.1016/s0163-8343(96)00109-0 · Cited by 439 · see citing works
Cloning and functional expression of a rat brain corticotropin releasing factor (CRF) receptor
Perrin, M. H., Donaldson, C. J., Chen, R., Lewis, K. A., & Vale, W. (1993) · Endocrinology · doi:10.1210/endo.133.6.8243338 · Cited by 437 · see citing works
Fukudo, S., Nomura, T., & Hongo, M. (1998) · Gut · doi:10.1136/gut.42.6.845 · Cited by 387 · see citing works
Self-citationWhitehead, W. E., & Delvaux, M. (1997) · Digestive Diseases and Sciences · doi:10.1023/a:1018885028501 · Cited by 387 · see citing works
Holsboer, F., von Bardeleben, U., & Steiger, A. (2008) · Neuroendocrinology · doi:10.1159/000124986 · Cited by 255 · cited 1× · see citing works
“This notion is supported by earlier reports indicating that intravenous administration of CRH influences sleep electroencephalo-grams in humans 39 and that blockage of central CRH receptors reduces spontaneous waking.”
ResultMaillot, C., Million, M., Wei, J. Y., Gauthier, A., & Taché, Y. (2000) · Gastroenterology · doi:10.1053/gast.2000.20251 · Cited by 206 · see citing works
Role of CRF in Stress‐Related Alterations of Gastric and Colonic Motor Functiona
Taché, Y., Mönnikes, H., Bonaz, B. L., & Rivier, J. (1993) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1993.tb49936.x · Cited by 206 · see citing works
Functional bowel disorders and functional abdominal pain
Thompson, W., Irvine, E., Drossman, D., et al. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/x3mq-ct28 · Cited by 204 · see citing works
Martı́nez, V., Rivier, J., Wang, L., & Taché, Y. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)36470-5 · Cited by 177 · see citing works
Postprandial colonic transit and motor activity in chronic constipation
Bazzocchi, G., Ellis, J., Villanueva‐Meyer, J., Jing, J., Reddy, S. N., Mena, I., & Snape, W. J. (1990) · Gastroenterology · doi:10.1016/0016-5085(90)90289-d · Cited by 170 · see citing works
Mönnikes, H., Schmidt, B. G., & Taché, Y. (1993) · Gastroenterology · doi:10.1016/0016-5085(93)91006-4 · Cited by 169 · see citing works
Gué, M., Junien, J., & Bueno, L. P. (1991) · Gastroenterology · doi:10.1016/0016-5085(91)90270-u · Cited by 144 · see citing works
CRF in the paraventricular nucleus mediates gastric and colonic motor response to restraint stress
Mönnikes, H., Schmidt, B. G., Raybould, H. E., & Taché, Y. (1992) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1992.262.1.g137 · Cited by 144 · see citing works
Perrin, M. H., Sutton, S. W., Cervini, L. A., Rivier, J., & Vale, W. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38013-9 · Cited by 142 · see citing works
Brain-Gut Response to Stress and Cholinergic Stimulation in Irritable Bowel Syndrome
Fukudo, S., Nomura, T., Muranaka, M., & Taguchi, F. (1993) · Journal of Clinical Gastroenterology · doi:10.1097/00004836-199309000-00009 · Cited by 124 · see citing works
Self-citationHiroi, N., Wong, M. L., Licinio, J., Park, C., Young, M., Gold, P. W., Chrousos, G. P., & Bornstein, S. R. (2001) · Molecular Psychiatry · doi:10.1038/sj.mp.4000908 · Cited by 124 · see citing works
Intestinal transit in anxiety and depression.
Gorard, D., Gomborone, J., Libby, G., & Farthing, M. (1996) · Gut · doi:10.1136/gut.39.4.551 · Cited by 124 · see citing works
Unidirectional Specific and Modulated Brain to Blood Transport of Corticotropin-Releasing Hormone
Martins, M., Kastin, A. J., & Banks, W. A. (2008) · Neuroendocrinology · doi:10.1159/000126974 · Cited by 119 · see citing works
Fukudo, S., & Suzuki, J. (1987) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.151.373 · Cited by 113 · see citing works
Self-citationBlockade of corticotropin-releasing hormone receptors reduces spontaneous waking in the rat
Chang, F., & Opp, M. R. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.275.3.r793 · Cited by 112 · see citing works
Functional Gastrointestinal Disorders
Banoub, H., Nazer, H. M., & Chong, S. K. F. (2012) · Springer eBooks · doi:10.1007/978-3-642-02202-9_185 · Cited by 107 · see citing works
Cold-restraint stress increases rat fecal pellet output and colonic transit
Barone, F. C., Deegan, J. F., Price, W. J., Fowler, P. J., Fondacaro, J. D., & Ormsbee, H. S. (1990) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1990.258.3.g329 · Cited by 106 · see citing works
Functional Gastrointestinal Disorders
Whorwell, P. J. (1995) · Gut · doi:10.1136/gut.36.2.320 · Cited by 101 · see citing works
nnikes, H., Schmidt, B. G., Tebbe, J. J., Bauer, C., & Taché, Y. (1994) · Brain Research · doi:10.1016/0006-8993(94)90352-2 · Cited by 89 · see citing works
Gastrointestinal disorders: Behavioral and physiological basis for treatment
Whitehead, W. E., & Schuster, M. M. (1985) · Medical Entomology and Zoology · Cited by 85 · see citing works
Cerebral electrical potentials evoked by balloon distention of the human esophagus
Castell, D. O., Wood, J. D., Frieling, T., et al. (1990) · Gastroenterology · doi:10.1016/0016-5085(90)90286-a · Cited by 77 · see citing works
Effects of the corticotropin‐releasing factor (CRF) on rectal afferent nerves in humans
Lembo, T., Plourde, V., Shui, Z., Fullerton, S. C., Mertz, H., Taché, Y., Sytnik, B., MUNAKATA, I., & Mayer, E. A. (1996) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.1996.tb00237.x · Cited by 76 · see citing works
Tougas, G. H., HUDOBA, P., Fitzpatrick, D., et al. (1993) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1993.264.3.g486 · Cited by 72 · see citing works
Abdominal surgery-induced delayed gastric emptying in rats: role of CRF and sensory neurons
Barquist, E. S., Zinner, M. J., Rivier, J., et al. (1992) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1992.262.4.g616 · Cited by 68 · see citing works
Motor activity recorded in the unprepared colon of healthy humans.
Lémann, M., Flourié, B., Picon, L., Coffin, B., Jian, R., & Rambaud, J. (1995) · Gut · doi:10.1136/gut.37.5.649 · Cited by 65 · see citing works
Fukudo, S., Kanazawa, M., Kano, M., Sagami, Y., Endo, Y., Utsumi, A., Nomura, T., & Hongo, M. (2002) · Journal of Gastroenterology · doi:10.1007/bf03326434 · Cited by 60 · see citing works
Self-citationIn vitro excitatory actions of corticotropin‐releasing factor on rat colonic motility
Mancinelli, R., Azzena, G. B., Diana, M., Forgione, A., & Fratta, W. (1998) · Journal of Autonomic Pharmacology · doi:10.1046/j.1365-2680.1998.1860319.x · Cited by 44 · see citing works
The effect of cold-restraint stress on gastric emptying in rats.
Koo, M., Ogle, C. W., & Chi, H.-C. (1985) · Pharmacology, Biochemistry and Behavior · doi:10.1016/0091-3057(85)90102-9 · Cited by 42 · see citing works
A Guide to gastrointestinal motility
Christensen, J. C., & Wingate, D. L. (1983) · Medical Entomology and Zoology · Cited by 40 · see citing works
Engin, H., Öksüzoğlu, B. Ç., & Altundağ, K. (2002) · Journal of Gastroenterology · doi:10.1007/s005350200012 · Cited by 15 · see citing works
Rectal Tone and Brain Information Processing in Irritable Bowel Syndrome
Blomhoff, S., Spetalen, S., Jacobsen, M., Vatn, M., & Malt, U. F. (2000) · Digestive Diseases and Sciences · doi:10.1023/a:1005550002622 · Cited by 11 · see citing works
Whitehead, W. E. (1985) · Medical Entomology and Zoology · Cited by 3 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Petrusz P, Merchenthaler I. The corticotropin-releasing factor system. In: Nemeroff CB, eds. Neuroendocrinology. Boca Raton, Florida: CRC Press, 1992:129-83.
- Fukudo S, Kotake M, Sagami Y, et al. Exaggerated viscerosensory evoked potentials in irritable bowel syndrome. Gastroenterology 2001;120:A4032.
- Fukudo S, Hongo M, Kanazawa M, et al. Colonic response to transmucosal electrical stimulation is impaired in patients with irritable bowel syndrome. Gastroenterology 1997;112:A1148.
Cited by
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Drossman, D. A. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.03.008 · Cited by 2,416 · see citing works
Vanuytsel, T., van Wanrooy, S., Vanheel, H., Vanormelingen, C., Verschueren, S., Houben, E., Salim Rasoel, S., Tόth, J., Holvoet, L., Farré, R., et al. (2014) · Gut · doi:10.1136/gutjnl-2013-305690 · Cited by 615 · see citing works
Jennings, E. M., Okine, B. N., Roche, M., & Finn, D. P. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2014.06.003 · Cited by 318 · see citing works
Elsenbruch, S., Rosenberger, C., Enck, P., Forsting, M., Schedlowski, M., & Gizewski, E. R. (2010) · Gut · doi:10.1136/gut.2008.175000 · Cited by 242 · see citing works
An Evidence-Based Systematic Review on the Management of Irritable Bowel Syndrome
Brandt, L. J., Chey, W. D., Foxx-Orenstein, A. E., Quigley, E. M. M., Schiller, L. R., Schoenfeld, P. S., Spiegel, B. M., Talley, N. J., & Moayyedi, P. (2009) · American Journal of Gastroenterology · doi:10.14309/00000434-200901001-00002 · Cited by 225 · see citing works
New insights into the pathogenesis and pathophysiology of irritable bowel syndrome
Öhman, L., & Simrén, M. (2007) · Digestive and Liver Disease · doi:10.1016/j.dld.2006.10.014 · Cited by 155 · see citing works
Brain and gut CRF signaling: biological actions and role in the gastrointestinal tract
Tache, Y., Larauche, M., Yuan, P.-Q., & Million, M. (2018) · Current Molecular Pharmacology · doi:10.2174/1874467210666170224095741 · Cited by 147 · see citing works
Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome
Ringel, Y., & Maharshak, N. (2013) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00207.2012 · Cited by 115 · see citing works
Recent developments in the therapy of irritable bowel syndrome
Saad, R. J., & Chey, W. D. (2008) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.17.2.117 · Cited by 21 · see citing works
- Authors
- Sagami, Y., Shimada, Y., Tayama, J., Nomura, T., Satake, M., Endo, Y., Shoji, T., Karahashi, K., Hongo, M., & Fukudo, S.
- Affiliations
- Tohoku University (JP)
- Corresponding author
- Fukudo, S
- ORCID
- Tayama, J
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2004-06-11
- Volume
- 53
- Issue
- 7
- Pages
- 958-964
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC1774093
- OpenAlex
- W2042968286
- Cited by
- 291
- References
- 44
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 10 · 2023: 9 · 2022: 9 · 2021: 11 · 2020: 5 · 2019: 6 · 2018: 6 · 2017: 7 · 2016: 12 · 2015: 15 · 2014: 18 · 2013: 15 · 2012: 16
- FWCI
- 16.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Health Professions › Pharmacy › Infant Health and Development
- Keywords
- irritable bowel syndrome, corticotropin-releasing factor, CRH receptor antagonist, colonic motility, visceral sensation, gut-brain axis, stress response, colonic distension, abdominal pain, anxiety, ACTH, cortisol, hypothalamic-pituitary-adrenal axis
- MeSH terms
- Adrenocorticotropic Hormone, Adult, Affect, Anxiety, Colon, Colonic Diseases, Functional, Corticotropin-Releasing Hormone, Electric Stimulation, Female, Gastrointestinal Agents, Gastrointestinal Motility, Humans, Hydrocortisone, Male, Muscle Tonus, Pressure, Sensation, Sensory Thresholds, Stress, Physiological, Abdominal Pain, Receptors, Corticotropin-Releasing Hormone
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