# Corticotropin-releasing factor and the brain-gut motor response to stress.



## eric (Jul 8, 1999)

Corticotropin-releasing factor and the brain-gut motor response to stress. Tache Y, Martinez V, Million M, Rivier J CURE: Digestive Diseases Research Center, West Los Angeles VA Medical Center, Los Angeles 90073, USA. ytache###ucla.edu The characterization of corticotropin-releasing factor (CRF) and CRF receptors, and the development of specific CRF receptor antagonists selective for the receptor subtypes have paved the way to the understanding of the biochemical coding of stress-related alterations of gut motor function. Reports have consistently established that central administration of CRF acts in the brain to inhibit gastric emptying while stimulating colonic motor function through modulation of the vagal and sacral parasympathetic outflow in rodents. Endogenous CRF in the brain plays a role in mediating various forms of stressor-induced gastric stasis, including postoperative gastric ileus, and activates colonic transit and fecal excretion elicited by psychologically aversive or fearful stimuli. It is known that brain CRF is involved in the cross-talk between the immune and gastrointestinal systems because systemic or central administration of interleukin-1-beta delays gastric emptying while stimulating colonic motor activity through activation of CRF release in the brain. The paraventricular nucleus of the hypothalamus and the dorsal vagal complex are important sites of action for CRF to inhibit gastric motor function, while the paraventricular nucleus of the hypothalamus and the locus coeruleus complex are sites of action for CRF to stimulate colonic motor function. The inhibition of gastric emptying by CRF may be mediated by the interaction with the CRF2 receptors, while the anxiogenic and colonic  motor responses may involve CRF1 receptors. Hypersecretion of CRF in the brain may contribute to the pathophysiology of stress-related exacerbation of irritable bowel syndrome.------------------ http://www.ibshealth.com/


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## JeanG (Oct 20, 1999)

Hi Eric:Thanks for posting this interesting article.







I've read it through twice, and it will take a few more times reading to understand.Is it that the CRF receptors are located in the brain and that's what affects the gut?JeanG


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## Mike NoLomotil (Jun 6, 2000)

JEANG:In answer to your question, partially yes.CRF activation as noted in the article resuults in specific changes in motility of the gut from central stimuli (the brain). Interleukin-1 causes the CRF to be produced and that results in the stimulus. Interleukin-1 is a mediator released by the immune system in a hypersensitivity reaction.This was described in the following tutorial from INRA's Dept. of Pharmacology in Toulouse, France.INRA is the Institut National de la Recherche Agronomique, a national scientific and technological research establishment under the auspices of the Ministry of Higher Education and Research of the French government. They have research dept.s of various soecialties throughout universities. medical schools, and other instituions throughout France. The Pharmacology Dept. has done extensive work in thsi area and the following tutorial from that Department explains the origin of this CRF phenomenon based upon the whole of current summative research. This should answer the question better than I can.---------------------------------------------MODULATION OF GASTROINTESTINAL MOTILITY BY INTERLEUKINS.L. Buï¿½noDepartment of Pharmacology, INRA, Toulouse, France.There is now mounting evidence that IL1b locally released during gut inflammatory processes may influence sensitivity and motility by acting directly on nerve terminals and intrinsic neurons, but also through an activation of local immunocytes. However, cytokines released at CNS level in response to peripheral inflammatory stimulus may also act on brain structures to influence gastrointestinal and colonic motility.The action of centrally administered IL1b is linked to the CNS release of prostaglandins and corticotropin-releasing factor (CRF), their release being mediated through activation of both adrenergic and nitrergic pathways. While brain prostaglandins are responsible of the IL1b-induced inhibition of the upper gut motility, IL1b evokes a colonic motor stimulation linked to the brain release of CRF and the subsequent activation of vasopressin containing neurons which activate efferent nerves and the peripheral release of 5HT.In septic shock, the upper gut motor inhibition following intraperitoneal administration of E. Coli endotoxin is, in part, linked to a vagally driven CNS release of IL1b. Similarly colonic transit and motor activation observed in antigenic challenge in ovalbumin sensitized rats or b-lactoglobulin-sensitized guinea pig are suppressed by centrally administered IL1-ra, a IL1 receptor antagonist, these effects being mimicked by central administration of IL1b.Alterations in colonic motility occurring 2 to 7 days after intraluminal infusion of TNBS are transiently suppressed by peripheral IL1-ra administration suggesting a permanent role of IL1b in maintaining abnormal colonic motor pattern in rats under inflammatory conditions.Prolonged rectal distension is associated with an overexpression of IL1b at brain level and the colonic secretory reflex initiated by rectal distension is abolished after intracerebroventricular but not systemic administration of IL1-ra. This result suggests that IL1b may be released in response to a non-infectious stimulus. Similarly stress-induced activation of the synthesis of mediators such as histamine by mucosal mast cell also depends upon the central release of IL1.We conclude that interleukins and particularly IL1 play a major role in the modulation of gut motility in physiopathological situations by acting at different level (afferent, and afferent nerves or brain) to modulate functional visceral


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