Corticotropin-releasing factor and the brain-gut motor response to stress.
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.
Taché
Y
Y
CURE: Digestive Diseases Research Center, West Los Angeles VA Medical Center, Los Angeles 90073, USA. ytache@ucla.edu
Martinez
V
V
Million
M
M
Rivier
J
J
D000818:Animals; D001921:Brain / Q000503:physiopathology; D003106:Colon / Q000503:physiopathology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D005746:Gastric Emptying / Q000502:physiology; D005769:Gastrointestinal Motility / Q000502:physiology*; D006801:Humans; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D013312:Stress, Physiological / Q000503:physiopathology*
D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone