A Ghrelin Receptor Agonist Is an Effective Colokinetic in Rats With Diet-Induced Constipation

Neurogastroenterol Motil. 2015 May;27(5):610-7. doi: 10.1111/nmo.12517. Epub 2015 Jan 19.

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.

Keywords: capromorelin; constipation; ghrelin; low-fiber diet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colon / drug effects*
  • Colon / pathology
  • Constipation*
  • Defecation / drug effects*
  • Dietary Fiber
  • Gastrointestinal Motility / drug effects*
  • Piperidines / pharmacology*
  • Pyrazoles / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Ghrelin / agonists*
  • Rectum / drug effects*
  • Rectum / pathology

Substances

  • CP 424391
  • Dietary Fiber
  • Piperidines
  • Pyrazoles
  • Receptors, Ghrelin