No abstract

No abstract

General introductionThe concept of visceral hypersensitivity is accepted as being germane to several functional gastrointestinal disorders (FGIDs). The causes or risk factors associated with this hypersensitivity are unclear. This article addresses the proposed mechanisms leading to hypersensitivity: from genetic to inflammatory disorders, from central to peripheral alterations of function. However, in order to place visceral hypersensitivity in a more global perspective as an aetiological factor for FGIDs, it also provides a review of recent evidence regarding the role of other peripheral mechanisms (the intraluminal milieu), as also genetic factors in the pathophysiology of these disorders. The article has been divided into five independent sections. The first three sections summarize the evidence of visceral hypersensitivity as a biological marker of functional gut disorders, the peripheral and central mechanisms involved, and the role of inflammation on hypersensitivity. In opposition to visceral hypersensitivity as an isolated phenomenon in functional gut disorders, the last two sections focus on the importance of peripheral mechanisms, like motor disturbances, specifically those resulting on altered transport of intestinal gas, and alterations of the intraluminal milieu and genetics.Keywords abdominal pain, functional gut disorders, irritable bowel syndrome, visceral hypersensitivity. VISCERAL HYPERSENSITIVITY: BIOLOGICAL MARKER, PERIPHERAL MECHANISMS AND HETEROGENEITY IntroductionVisceral hypersensitivity is currently the leading hypothesis to explain irritable bowel syndrome (IBS) and other functional gastrointestinal disorders (FGIDs). After years of disappointing research trying to establish a correlation between the increased motor activity of the gut and the painful cramps felt by IBS patients, the theory that pain could be related to enhanced visceral sensitivity was raised. Ritchie, 1 in 1973, first reported that IBS patients were more sensitive than normal subjects to balloon distension of the colon. This observation of increased visceral sensitivity in IBS patients was confirmed by many researchers including Whitehead et al. 2 , Mertz et al. 3 and others. In agreement with the hypersensitivity of the colon found in IBS patients, intolerance to gastric distension was also documented in patients with functional dyspepsia (FD). 4-6Visceral hypersensitivity: biological marker of FGID?Mertz et al. 3 proposed that Ôaltered rectal perception is a biological marker of patients with IBSÕ as it was identified in 94 of 100 IBS patients studied by a rectal distension by barostat. We collected rectal distension data by an electronic barostat in 164 patients (86 IBS, 26 painless constipation, 21 FD and 31 others with miscellaneous conditions), 7 as also in 25 normal controls evaluated. As expected ( thresholds to rectal distension were lower in patients with IBS when compared with control subjects; they were also lower than in patients with painless constipation, FD or other miscellaneous conditions. Assuming ...

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...

Nodular adrenal hyperplasia and Cushing's syndrome may be food-dependent as a result of abnormal responsiveness of adrenal cells to physiologic secretion of GIP. "Illicit" (ectopic) expression of GIP receptors on adrenal cells presumably underlies this disorder.