Published online Jun 7, 2017. doi: 10.3748/wjg.v23.i21.3825
Peer-review started: November 25, 2016
First decision: December 19, 2016
Revised: January 18, 2017
Accepted: April 13, 2017
Article in press: April 13, 2017
Published online: June 7, 2017
To measure exogenous corticotropin-releasing factor (CRF)-induced motility of the isolated rat colon and to demonstrate the effect of pharmacologic inhibition on CRF-induced motility.
The isolated vascularly-perfused rat colon was used. Luminal pressure was monitored via microtip catheter pressure transducers in the proximal and distal colon. At first, exogenous CRF was administered in a stepwise manner and the concentration of CRF yielding maximal colonic motility was selected. After recording basal colonic motility, hexamethonium, phentolamine, propranolol, atropine and tetrodotoxin were infused into the isolated colon. Initially, only the test drug was infused; then, CRF was added. The motility index was expressed as percentage change over basal level.
Administration of 1.4, 14.4, 144 and 288 pmol/L CRF progressively increased colonic motility in the proximal and distal colon. Infusion of atropine or tetrodotoxin reduced CRF-induced motility of both the proximal and distal colon, whereas hexamethonium, phentolamine and propranolol had no effect.
CRF-induced colonic motility appears to be mediated by local cholinergic signaling via muscarinic receptors. Muscarinic receptors are potential targets for counteracting CRF-induced colonic hypermotility.
Core tip: Corticotropin-releasing factor (CRF) has emerged as a key mediator of functional bowel disorders and the effects of stress and inflammation on the gastrointestinal tract. CRF-induced colonic motility is mediated by local cholinergic signaling via muscarinic receptors, and blocking muscarinic receptors is a potential way to prevent CRF-induced hypermotility of the colon.