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.