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

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 μg/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 μg/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-[Gln14]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 μg/kg iv). In rats in which postoperative gastrointestinal ileus had been experimentally induced, ghrelin/MTLRP (20 μg/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.