motilin and Irritable-Bowel-Syndrome

Renzapride is a novel drug currently under clinical evaluation for the treatment of irritable bowel syndrome (IBS). Renzapride is a mixed 5-hydroxytryptamine type 4 (5-HT4) agonist and 5-HT3 receptor antagonist that has a stimulatory effect on gastrointestinal motility and transit, as established by in vivo and in vitro studies. Its therapeutic efficacy, tolerability and safety have been evaluated in diabetic gastroparesis in a single study, as well as in IBS in a few other studies. Phase II studies indicated potential beneficial effects on symptoms and bowel habits in patients with constipation-predominant IBS and mixed-type IBS. The outcome of Phase III studies is currently under evaluation.

Topics: Animals; Benzamides; Bridged Bicyclo Compounds, Heterocyclic; Constipation; Gastrins; Humans; Irritable Bowel Syndrome; Motilin

Sensory and motor dysfunctions of the gut are both important characteristics of irritable bowel syndrome (IBS). Several gut peptides contribute to the regulation of gastrointestinal function but little is known about gut hormone secretion in IBS.. We evaluated perceptual thresholds and fasting and postprandial plasma levels of proximal (cholecystokinin (CCK), motilin) and distal (peptide YY) gut peptides up to 1 h after ingestion of a high caloric meal in 99 IBS patients and 40 age- and gender-matched healthy controls.. Fasting plasma CCK levels were significantly elevated in patients (1.2+/-0.8 pM) compared with those in controls (0.8+/-0.7 pM, p=0.006), as was the incremental postprandial CCK response (72+/-73 versus 40+/-42 pM.60 min, respectively; p=0.003). No differences in fasting and postprandial motilin or PYY levels were found. The postprandial PYY response was significantly increased in hypersensitive compared to normosensitive patients (215+/-135 versus 162+/-169 pM, p=0.048). Patients with a diarrhoea predominant bowel habit had higher fasting motilin levels compared to constipated patients or alternating type IBS patients (82.1+/-36.5 versus 60.8+/-25.1 versus 57.5+/-23.9 pM, one-way ANOVA p=0.003).. IBS patients have increased fasting and postprandial plasma levels of CCK. Changes in plasma levels of motilin and PYY may contribute to the clinical expression of IBS, such as the presence of visceral hypersensitivity or a predominant bowel habit.

Topics: Adolescent; Adult; Age Factors; Aged; Biomarkers; Cholecystokinin; Fasting; Female; Follow-Up Studies; Humans; Intestine, Small; Irritable Bowel Syndrome; Male; Middle Aged; Motilin; Peptide YY; Postprandial Period; Psychotherapy; Radioimmunoassay; Retrospective Studies; Sex Factors

Motilin shows cyclic variation with the different phases of the migrating motor complex (MMC). Altered motilin levels have been found in irritable bowel syndrome (IBS) patients, but in these studies motilin levels were analysed without the knowledge of the phases of MMC. We included 13 healthy controls (HC) and 24 patients with IBS [12 diarrhoea-predominant (IBS-D) and 12 constipation-predominant (IBS-C)]. We performed interdigestive and postprandial antroduodenojejunal manometry and blood samples for analysis of motilin were drawn. Group differences in plasma levels of motilin were analysed during mid-phase II, just before the start of phase III (pre-III), during phase I, immediately before the meal and 30 and 60 min after the 500 kcal mixed meal. Higher motilin levels were observed in IBS vs HC in both the interdigestive and postprandial periods (P < 0.05). No significant differences between IBS-C and IBS-D were observed. The cyclic variation of motilin during MMC and the meal response was similar in IBS and controls. IBS patients, irrespective of the predominant bowel habit, demonstrate higher motilin levels than HCs in all phases of the MMC and also after a meal. These findings may bear some pathophysiological importance in IBS and relate to the gastrointestinal dysmotility often seen in these patients.

Topics: Adult; Aged; Constipation; Digestion; Female; Humans; Irritable Bowel Syndrome; Male; Manometry; Middle Aged; Motilin; Myoelectric Complex, Migrating; Postprandial Period

The aim of this study was to investigate the mechanism (s) of action of gastrointestinal hormones in the pathogenesis of irritable bowel syndrome (IBS), and the correlation between gastrointestinal hormones and psychological factors. Patients with IBS were divided into IBS with normal emotional state ratings and IBS in anxiety-depressive states groups. The two groups were then subdivided into IBS-constipation predominant (IBS-C) and IBS-diarrhea predominant (IBS-D) groups. Non-IBS patients with normal depression and anxiety ratings were recruited as controls. The expression of somatostatin (SS) and vasointestinalpeptid (VIP), motilin in the colonic mucosa was detected by immunohistochemistry and radioimmunoassay. The anxiety-depression scores of patients with IBS were significantly different from those of the control group. The expression levels of SS and VIP, motilin colonic mucosa of the patients with IBS were higher compared with those of the control.group. Furthermore, the expression level of SS in the IBS-C group demonstrated a significantly larger increase than that in the IBS-D group; however, there was no significant difference in the expression of VIP between the IBS-C and IBS-D groups. In addition, the expression levels of SS and VIP, motilin in the IBS groups with normal emotional state ratings were notably different from those in the IBS groups in anxiety-depressive states. Anxiety-depressive states may lead to changes in the secretion of SS and VIP, motilin, and subsequently to changes in gastrointestinal motility and function.

Topics: Adolescent; Adult; Anxiety Disorders; Colon; Depression; Female; Gastrointestinal Motility; Gene Expression Regulation; Humans; Intestinal Mucosa; Irritable Bowel Syndrome; Male; Middle Aged; Motilin; Neurosecretory Systems; Somatostatin; Vasoactive Intestinal Peptide

We have previously shown that ghrelin is mainly localized to the stomach but also occurs, together with the prokinetic hormone motilin, in endocrine cells in the proximal small intestine. This study explored ghrelin and motilin concentrations in plasma in relation to gastrointestinal motility and whether plasma ghrelin is changed in patients with irritable bowel syndrome (IBS). Nine patients with severe IBS and 10 healthy subjects underwent stationary antro-duodeni-jejunal manometry; blood was sampled during similar motility phases in the two groups. The motility phases were monitored and blood samples were collected during fasting and after food intake. Plasma was analyzed for two forms of ghrelin (octanylated and desoctanylated) as well as for motilin. In IBS patients circulating motilin levels covaried with total ghrelin levels (r=0.90; p<0.004), octanylated ghrelin (r=0.77; p<0.02) and desoctanylated ghrelin (r=0.69; p<0.04). No such correlations were seen in the control group. Octanylated ghrelin comprised 35.3+/-3.9% (mean+/-SEM) of the total circulating ghrelin in the IBS patients compared to 40.4+/-4.5% (mean+/-SEM) in the control group (NS). Ghrelin covaried with motilin in plasma in IBS but not in plasma from healthy subjects. This suggests the two peptides act together in IBS.

Topics: Eating; Fasting; Ghrelin; Humans; Irritable Bowel Syndrome; Manometry; Motilin; Myoelectric Complex, Migrating

Topics: Cholecystokinin; Emotions; Humans; Irritable Bowel Syndrome; Motilin; Music; Vascular Endothelial Growth Factor A