Article

Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome

Department of Psychosomatic Medicine, Tohoku University School of Medicine, Sendai, Japan.
Gut (Impact Factor: 13.32). 08/2004; 53(7):958-64. DOI: 10.1016/S0016-5085(03)82897-4
Source: PubMed

ABSTRACT 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 alpha-helical CRH (alphahCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients.
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 alphahCRH (10 micro g/kg).
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 alphahCRH. Administration of alphahCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. alphahCRH 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 alphahCRH.
Peripheral administration of alphahCRH 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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Available from: Jun Tayama, Aug 14, 2015
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    • "CRH expression and biological function are mediated by its membrane receptors, CRH-R1 and CRH-R2 (Grammatopoulos, 2012). CRH is involved in the pathogenesis of a number of inflammatory disorders, such as allergic diseases (Vasiadi et al., 2012), irritable bowel syndrome (Sagami et al., 2004) and some pain syndromes (La et al., 2008). CRH can also activate microglia in the process of neuropathology (Wang et al., 2007), but the underlying mechanism is not fully understood. "
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    • "Deletion of the CRF 1 gene using transgenic models or intraventricular administered CRF 1 antagonists have anxiolytic affects and attenuate stress-and CRF-induced alterations in gastric and colonic motor function (Million et al., 2003; Trimble et al., 2007). Moreover, recent clinical investigations have shown that intravenously administered CRF increases gastrointestinal motility and visceral pain sensitivity in IBS patients compared to healthy controls (HCs), while administration of a non-selective CRF receptor antagonist ameliorated these responses (Lembo et al., 1996; Fukudo et al., 1998; Sagami et al., 2004). Taken together, these findings have spurred the development of novel and highly selective CRF 1 antagonists as candidate drugs for treatment of IBS (Zorrilla and Koob, 2010). "
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