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

Author(s): Jozsef Czimmer, Yvette Tache*

Journal Name: Current Pharmaceutical Design

Volume 23 , Issue 27 , 2017


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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.

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

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Article Details

VOLUME: 23
ISSUE: 27
Year: 2017
Published on: 29 October, 2017
Page: [4042 - 4047]
Pages: 6
DOI: 10.2174/1381612823666170228142428
Price: $65

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