Ghrelin/motilin-related peptide is a potent prokinetic to reverse gastric postoperative ileus in rat

Am J Physiol Gastrointest Liver Physiol. 2002 Jun;282(6):G948-52. doi: 10.1152/ajpgi.00339.2001.

Abstract

A novel peptide called ghrelin or motilin-related-peptide (MTLRP) was found in the stomach of various mammals. We studied its effect on the motor function of the rat gastrointestinal tract. In normal, conscious unoperated animals, ghrelin/MTLRP (5 or 20 microg/kg iv) significantly accelerated the gastric emptying of a methylcellulose liquid solution (gastric residue after 15 min: 57 +/- 7, 42 +/- 11, 17 +/- 4, and 9 +/- 3% of the ingested meal with doses of 0, 1, 5, and 20 microg/kg iv, respectively) Transit of the methylcellulose liquid solution was also accelerated by ghrelin/MTLRP in the small intestine but not in the colon. Des-[Gln(14)]ghrelin, also found in the mammalian stomach, was as potent as ghrelin in emptying the stomach (gastric residue after 15 min: 12 +/- 3% at a dose of 20 microg/kg iv). In rats in which postoperative gastrointestinal ileus had been experimentally induced, ghrelin/MTLRP (20 microg/kg iv) reversed the delayed gastric evacuation (gastric residue after 15 min: 28 +/- 7% of the ingested meal vs. 82 +/- 9% with saline). In comparison, the gastric ileus was not modified by high doses of motilin (77 +/- 7%) or erythromycin (82 +/- 6%) and was only partially improved by calcitonin gene-related peptide (CGRP) 8-37 antagonist (59 +/- 7%). Ghrelin/MTLRP, therefore, accelerates the gastric emptying and small intestinal transit of a liquid meal and is a strong prokinetic agent capable of reversing the postoperative gastric ileus in rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colon / drug effects
  • Colon / physiology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Gastric Emptying / drug effects
  • Gastrointestinal Motility / drug effects
  • Ghrelin
  • Intestinal Obstruction / drug therapy*
  • Intestine, Small / drug effects
  • Intestine, Small / physiology
  • Male
  • Motilin / pharmacology*
  • Peptide Hormones*
  • Peptides / pharmacology*
  • Postoperative Complications / drug therapy*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Ghrelin
  • Peptide Hormones
  • Peptides
  • ghrelin, des-Gln(14)-
  • Motilin