Peripherally administered CRF stimulates colonic motility via central CRF receptors and vagal pathways in conscious rats

Abstract

Corticotropin releasing factor (CRF) is one of the most important factors in the mechanism of stress-induced stimulation of colonic motility. However, it is controversial whether stress-induced stimulation of colonic motility is mediated via central or peripheral CRF receptors. We investigated the hypothesis that peripherally injected CRF accelerates colonic motility through the central CRF receptor, but not the peripheral CRF receptor. A strain gauge transducer was sutured on the serosal surface of the proximal colon. Colonic motility was monitored before and after the peripheral injection of CRF. An in vitro muscle strip study was also performed to investigate the peripheral effects of CRF. Subcutaneous injection of CRF (30 -100 g/kg) stimulated colonic motility in a dose-dependent manner. The stimulatory effect of peripherally administered CRF on colonic motility was abolished by truncal vagotomy, hexamethonium, atropine, and intracisternal injection of astressin (a CRF receptor antagonist). No responses to CRF (10 Ϫ9 Ϫ10 Ϫ7 M) of the muscle strips of the proximal colon were observed. These results suggest that the stimulatory effect of colonic motility in response to peripheral administration of CRF is mediated by the vagus nerve, nicotinic receptors, muscarinic receptors, and CRF receptors of the brain stem. It is concluded that peripherally administered CRF reaches the area postrema and activates the dorsal nucleus of vagi via central CRF receptors, resulting in stimulation of the vagal efferent and cholinergic transmission of the proximal colon.vagal efferent THERE IS ACCUMULATED EVIDENCE that stress stimulates the release of corticotropin releasing factor (CRF) from the paraventricular nucleus and that released CRF stimulates colonic motor activity. However, it is controversial whether CRF-induced acceleration of colonic motility is mediated via central CRF receptors (4) or peripheral CRF receptors (3). Stress or centrally injected CRF stimulates colonic motor function by cerebral CRF receptors (10,22). The stimulatory effect of centrally administered CRF on colonic transit is abolished by truncal vagotomy (9). Electrophysiological study demonstrated that CRF stimulates the dorsal motor nucleus of the vagus nerve (DMV) in vivo and in vitro (11). Stress-induced stimulation of defecatory response is antagonized by the central administration of a CRF antagonist, but not by the peripheral administration of a CRF antagonist (16). These reports indicated that centrally released CRF induced by stress stimulates vagal efferent, resulting in stimulation of colonic motility and transit.In contrast, others showed that peripherally administered CRF stimulates colonic motility via its own peripheral receptor, and the stimulatory effect of CRF is antagonized by peripheral injection of CRF antagonists (13,14,26). Restraint stress-induced stimulation of fecal pellet output is antagonized by the peripheral administration of a CRF antagonist (26). CRF-producing cells are present in the colonic mucosa (7,19). It is propose...

The structures of the colonic mucosa-associated and luminal microbial communities are distinct and differentially affected by a prolonged murine stressor

“…In an olfactory bulbectomy model of stressor sensitization, Park et al (2013) demonstrated that stressor-induced increases in colonic motility impact microbiota structure through a corticotrophin-releasing hormone (CRH)-dependent mechanism. 85 Because CRH-induced alterations in colonic motility can be disrupted by cutting the vagal nerve 86 , and because the vagus nerve is considered a primary route through which the brain and gut microbiota interact [87][88][89] , it is possible that the observed stressorinduced changes in the colonic microbiota are vagally-mediated. This hypothesis warrants further attention.…”

The Irritable Bowel Syndrome: How Stress Can Affect the Amygdala Activity and the Brain-Gut Axis

“…At the peripheral level, mast cells degranulation observed in the colon following stress and peripheral administration of CRF (Wallon, et al 2008) induces visceral hypersensitivity via the release of mediators (histamine, tryptase, prostaglandin E2, nerve growth factor) that can stimulate or sensitize sensory afferents (van den Wijngaard, et al 2009;2010). Intravenous administration of CRF increases GI motility and visceral pain sensitivity in IBS patients compared with healthy controls, whereas administration of a non-selective CRF receptor antagonist improved these responses Tache, et al 2005;Tsukamoto, et al 2006). …”

Role of Corticotropin-releasing Factor Signaling in Stress-related Alterations of Colonic Motility and Hyperalgesia

“…Functional studies showed that CRF and Ucn1 injected peripherally are as potent as injected centrally to increase propagative clustered spike-burst activity in the proximal colon and to stimulate distal colonic transit, defecation and to induce prominent diarrhea in rodents. 54,72,76,[108][109][110][111][112][113][114][115] The stimulation of colonic secretory-motor function after peripheral administration of CRF or Ucn1 involves CRF 1 receptors in rats and mice. This is supported by the fact that elective CRF 1 agonist, cortagine or stressin1 injected intraperitoneally stimulates colonic motor function and induces diarrhea while the CRF 2 agonists, Ucn2 has not effect under the same conditions.…”