Ghrelin/motilin-related peptide is a potent prokinetic to reverse gastric postoperative ileus in rat.
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.
Trudel
L
L
Department of Gastroenterology, Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
Tomasetto
C
C
Rio
M C
MC
Bouin
M
M
Plourde
V
V
Eberling
P
P
Poitras
P
P
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005746:Gastric Emptying / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects; D054439:Ghrelin; D007415:Intestinal Obstruction / Q000188:drug therapy*; D007421:Intestine, Small / Q000187:drug effects / Q000502:physiology; D008297:Male; D009037:Motilin / Q000494:pharmacology*; D036361:Peptide Hormones; D010455:Peptides / Q000494:pharmacology*; D011183:Postoperative Complications / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
D054439:Ghrelin; D036361:Peptide Hormones; D010455:Peptides; C412225:ghrelin, des-Gln(14)-; D009037:Motilin