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

Abstract

Trudel, L., C. Tomasetto, M. C. Rio, M. Bouin M, V. Plourde, P. Eberling, and P. Poitras. Ghrelin/motilinrelated peptide is a potent prokinetic to reverse gastric postoperative ileus in rat. Am J Physiol Gastrointest Liver Physiol 282: G948-G952, 2002; 10.1152/ajpgi.00339.2001.-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 g/kg iv) significantly accelerated the gastric emptying of a methylcellulose liquid solution (gastric residue after 15 min: 57 Ϯ 7, 42 Ϯ 11, 17 Ϯ 4, and 9 Ϯ 3% of the ingested meal with doses of 0, 1, 5, and 20 g/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 Ϯ 3% at a dose of 20 g/kg iv). In rats in which postoperative gastrointestinal ileus had been experimentally induced, ghrelin/MTLRP (20 g/kg iv) reversed the delayed gastric evacuation (gastric residue after 15 min: 28 Ϯ 7% of the ingested meal vs. 82 Ϯ 9% with saline). In comparison, the gastric ileus was not modified by high doses of motilin (77 Ϯ 7%) or erythromycin (82 Ϯ 6%) and was only partially improved by calcitonin gene-related peptide (CGRP) 8-37 antagonist (59 Ϯ 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. regulatory peptides; gastrointestinal hormones; gastrointestinal motility A NOVEL PEPTIDE WAS IDENTIFIED recently in endocrine cells of the gastric mucosa of mouse, rat, dog, and human (9,20,22). It was discovered simultaneously by two research teams who named it, respectively, motilin-related peptide (MTLRP) and ghrelin. Tomasetto et al. (21) used molecular biology to look for new proteins of the gastric epithelium that could provide insight to the differentiation and function of the gastric unit. They discovered a protein expressed in secretory granules of the mouse stomach endocrine cells in which chromogranin A, serotinin, and somatostatin also colocalized. The protein has sequence similarity (47%) with prepromotilin, and the secreted peptide was, therefore, tentatively named motilin-related peptide. At the same time, Japanese researchers (9), looking for an endogenous ligand for growth hormone secretagoge receptor, purified and identified from rat stomach a peptide of 28 amino acids they called ghrelin (ghre is the proto-IndoEuropean root of the word grow). Ghrelin is now most often used to identify the peptide.Because it interacts with the growth hormone secretagoge receptor of the pituitary, ghrelin has definite actions on the release of growth hormone (9,18,20,24), but also on appetite stimulation (counterbalancin...

Plasma ghrelin levels in healthy elderly volunteers: the levels of acylated ghrelin in elderly females correlate positively with serum IGF-I levels and bowel movement frequency and negatively with systolic blood pressure

“…It should be noted that the smaller number of men than women might have resulted in the borderline correlation between male acylated ghrelin level and the frequency of bowel movement. Ghrelin administration in humans stimulates peristalsis (Takaya et al 2000, Nagaya et al 2001, Akamizu et al 2004) and enhances gastric and intestinal motilities in rats (Masuda et al 2000, Trudel et al 2002, Fujino et al 2003. These findings suggest that ghrelin might play a role in the regulation of bowel motility.…”

“…Ghrelin, a 28-amino-acid peptide, exhibits a variety of actions, including vasorelaxation (Nagaya et al 2001, Shimizu et al 2003 and stimulation of GH secretion (Takaya et al 2000, Arvat et al 2001, Hataya et al 2001, appetite (Korbonits et al 2004, van der Lely et al 2004 and gastrointestinal motility (Masuda et al 2000, Trudel et al 2002, Fujino et al 2003. A portion of ghrelin possesses a unique fatty acid modification, n-octanoylation, at Ser 3 (Kojima et al 1999).…”

Possible entrainment of ghrelin to habitual meal patterns in humans

“…It is released following cephalic stimulation (1); the sites for its synthesis are proximal (10,22,24); and it stimulates gastric acid secretion (11,26), gastrointestinal motility (13,38), and pancreatic exocrine secretions (32), all of which increase in anticipation of eating. Indeed, stimulating these physiological responses may be ghrelin's primary feedingrelated function.…”

Therapeutic Applications of Ghrelin Agonists in the Treatment of Gastroparesis

“…Meanwhile, consistent reports of effects of ghrelin on colonic contractility have been lacking despite tissue expression of GRLN-R [58][59][60][61][62]. Animal studies in dogs and rodents have shown no effect on colonic motility with intravenous administration of ghrelin, while central or intraperitoneal administration has demonstrated stimulation of colonic motility reflected by decreased colonic transit time and increased intracolorectal pressures and fluid output [63][64][65][66][67], suggesting that effects of ghrelin or ghrelin agonists on colonic motility are centrally mediated, requiring crossing of the blood brain barrier.…”