R V Pustovit1, J B Furness, L R Rivera. 1. Department of Anatomy & Neuroscience, University of Melbourne, Parkville, VIC, Australia.
Abstract
BACKGROUND: Despite constipation being a common problem, the treatments that are available have side effects and are only partly effective. Recent studies show that centrally penetrant ghrelin receptor agonists cause defecation in humans and other species. Here, we describe some features of a rat model of low fiber-induced constipation, and investigate the effectiveness of the ghrelin agonist, capromorelin. METHODS: Rats were given low-fiber diets for 5 weeks. Their colorectal responsiveness to distension and to a behavioral test, water avoidance and colon histology were compared to those of rats on a standard diet. KEY RESULTS: After the low-fiber diet, distension of the colon produced fewer propulsive contractions, behaviorally induced defecation was reduced, and the lining of the colorectum was inflamed. However, capromorelin was similarly effective in causing defecation in constipated and non-constipated rats. CONCLUSIONS & INFERENCES: Low-fiber diet in rats produces a constipation phenotype, characterized by reduced responsiveness of the colorectum to distension and to a behavioral stimulus of defecation, water avoidance. The effectiveness of capromorelin suggests that centrally penetrant ghrelin receptor stimulants may be effective in treating constipation.
BACKGROUND: Despite constipation being a common problem, the treatments that are available have side effects and are only partly effective. Recent studies show that centrally penetrant ghrelin receptor agonists cause defecation in humans and other species. Here, we describe some features of a rat model of low fiber-induced constipation, and investigate the effectiveness of the ghrelin agonist, capromorelin. METHODS:Rats were given low-fiber diets for 5 weeks. Their colorectal responsiveness to distension and to a behavioral test, water avoidance and colon histology were compared to those of rats on a standard diet. KEY RESULTS: After the low-fiber diet, distension of the colon produced fewer propulsive contractions, behaviorally induced defecation was reduced, and the lining of the colorectum was inflamed. However, capromorelin was similarly effective in causing defecation in constipated and non-constipatedrats. CONCLUSIONS & INFERENCES: Low-fiber diet in rats produces a constipation phenotype, characterized by reduced responsiveness of the colorectum to distension and to a behavioral stimulus of defecation, water avoidance. The effectiveness of capromorelin suggests that centrally penetrant ghrelin receptor stimulants may be effective in treating constipation.
Authors: Ruslan V Pustovit; Brid Callaghan; Mitchell T Ringuet; Nicole F Kerr; Billie Hunne; Ian M Smyth; Claudio Pietra; John B Furness Journal: Physiol Rep Date: 2017-08
Authors: Gianfabio Giorgioni; Fabio Del Bello; Wilma Quaglia; Luca Botticelli; Carlo Cifani; E Micioni Di Bonaventura; M V Micioni Di Bonaventura; Alessandro Piergentili Journal: J Med Chem Date: 2022-02-14 Impact factor: 7.446