Peripheral Corticotropin Releasing Factor Signaling Inhibits Gastric Emptying: Mechanisms of Action and Role in Stress-related Gastric Alterations of Motor Function

Title:Peripheral Corticotropin Releasing Factor Signaling Inhibits Gastric Emptying: Mechanisms of Action and Role in Stress-related Gastric Alterations of Motor Function

Volume: 23 Issue: 27

Author(s): Jozsef Czimmer and Yvette Tache*

Affiliation:

• CURE: Digestive Diseases Research Center, Building 115, Room 117, VA Greater Los Angeles Healthcare System, 11301 Wilshire Boulevard, Los Angeles, CA 90073,United States

Keywords: CRF, CRF receptor, gastric emptying, stress, urocortin.

Abstract: The activation of Corticotrophin Releasing-Factor (CRF) receptors in the brain is well established to coordinate the endocrine, behavioral, autonomic and visceral responses to stress. In addition, CRF receptors are also expressed within the gut where they exert biological actions and play a role in modulating stress-related gastrointestinal function. In particular, peripheral injection of CRF and related peptides, urocortin 1, 2 or 3 inhibit Gastric Emptying (GE) and alters fasted and fed pattern of gastroduodenal motility in several experimental species. Urocortin 1 interacts synergistically with cholecystokin-8 to inhibit gastric emptying in lean mice which is no longer observed in diet-induced obese rats. In in vitro circular or longitudinal muscle preparation of rat antrum, CRF and urocortin 1 and 2 suppressed spontaneous contractile activity. CRF and urocortins interact with the CRF receptor 2 (CRF-R2) to inhibit gastric motor function monitored both in vivo and in vitro. The CRF-R2 mediated inhibition of antral and corpus contractility involves a direct action on gastric myenteric neurons where CRF-R2 is expressed and may also involve the activation of serotonin acting on 5-HT3 receptor. The involvement of peripheral CRF receptors in gastric motor alterations occurring under stress conditions are stressors specific with CRF-R2 mediating the early phase of gastric ileus induced by abdominal surgery and the delayed emptying elicited by acute restraint stress. However gastric stasis elicited by endotoxin is not mediated by CRF-R2 and CRF receptors are not involved in the basal regulation of fed or fasted pattern of gastric motility.

Cite this article as:

Czimmer Jozsef and Tache Yvette*, Peripheral Corticotropin Releasing Factor Signaling Inhibits Gastric Emptying: Mechanisms of Action and Role in Stress-related Gastric Alterations of Motor Function, Current Pharmaceutical Design 2017; 23 (27) . https://dx.doi.org/10.2174/1381612823666170228142428