motilin and Constipation

The gastrointestinal tract is the major source of the related hormones ghrelin and motilin, which act on structurally similar G protein-coupled receptors. Nevertheless, selective receptor agonists are available. The primary roles of endogenous ghrelin and motilin in the digestive system are to increase appetite or hedonic eating (ghrelin) and initiate phase III of gastric migrating myoelectric complexes (motilin). Ghrelin and motilin also both inhibit nausea. In clinical trials, the motilin receptor agonist camicinal increased gastric emptying, but at lower doses reduced gastroparesis symptoms and improved appetite. Ghrelin receptor agonists have been trialled for the treatment of diabetic gastroparesis because of their ability to increase gastric emptying, but with mixed results; however, relamorelin, a ghrelin agonist, reduced nausea and vomiting in patients with this disorder. Treatment of postoperative ileus with a ghrelin receptor agonist proved unsuccessful. Centrally penetrant ghrelin receptor agonists stimulate defecation in animals and humans, although ghrelin itself does not seem to control colorectal function. Thus, the most promising uses of motilin receptor agonists are the treatment of gastroparesis or conditions with slow gastric emptying, and ghrelin receptor agonists hold potential for the reduction of nausea and vomiting, and the treatment of constipation. Therapeutic, gastrointestinal roles for receptor antagonists or inverse agonists have not been identified.

Topics: Appetite; Constipation; Gastric Emptying; Gastrointestinal Agents; Gastrointestinal Diseases; Gastrointestinal Motility; Ghrelin; Humans; Hunger; Motilin; Nausea; Receptors, Gastrointestinal Hormone; Receptors, Ghrelin; Receptors, Neuropeptide; Signal Transduction

Chronic constipation is a common digestive problem in North America, with significant psychosocioeconomic implications. Dietary and lifestyle measures and low-cost traditional over-the-counter laxatives are usually the first line of therapy but help only half of the patients. Several newer agents that act by increasing colonic peristalsis, altering colonic secretion, and/or antagonizing enteric opioid receptors have been developed that are effective in treating constipation and its related symptoms as well as improving quality of life. This article focuses on the pharmacology of traditional and newer agents for the treatment of constipation.

Topics: Alprostadil; Chronic Disease; Colchicine; Constipation; Guanylate Cyclase; Humans; Laxatives; Lubiprostone; Motilin; Narcotic Antagonists; Neurotrophin 3; Prebiotics; Probiotics; Receptors, Enterotoxin; Receptors, Guanylate Cyclase-Coupled; Receptors, Peptide; Surface-Active Agents

Chronic constipation (CC) is one of the most common functional gastrointestinal disorders. CC is estimated to affect up to 27% of the North American population. Although not life-threatening, CC can have profoundly negatively affects on quality of life and result in significant economic burden in terms of both direct and indirect healthcare costs. Possible etiologies for CC include alterations in gastrointestinal motility and secretion. Research efforts in CC have begun to identify multifactorial and often overlapping etiologies including abnormalities in myenteric neurons, alterations in neurotransmitters and their receptors, and incoordination of the muscles of the pelvic floor or anorectum. CC may be influenced by genetic predisposition, environmental factors and stress. In this article, the safety and efficacy of traditional and emerging therapies for CC are examined.

Topics: Analgesics, Opioid; Cathartics; Chloride Channel Agonists; Chronic Disease; Constipation; Drug Discovery; Gastrointestinal Motility; Humans; Motilin; Narcotic Antagonists; Natriuretic Peptides; Serotonin Agents

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

Topics: Biomarkers; Constipation; Diabetes Mellitus; Diagnostic Techniques, Endocrine; Diarrhea; Duodenal Ulcer; Gastrointestinal Motility; Humans; Inflammatory Bowel Diseases; Kidney Failure, Chronic; Motilin; Radioimmunoassay; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide; Reference Values; Specimen Handling

To compare the efficacy between acupuncture with smoothing liver and regulating. Sixty patients were randomized into an acupuncture group and a medication group,30 cases in each one. Based on the comprehensive stroke unit care,acupuncture with smoothing liver and regulating. The time of the first independent defecation was (30.18±16.14) h in the acupuncture group,which was significantly different from (43.22±28.42) h in the medication group(. Acupuncture with smoothing liver and regulating

Topics: Acupuncture Points; Acupuncture Therapy; Constipation; Gastrointestinal Agents; Humans; Lactulose; Liver; Motilin; Qi; Somatostatin; Stroke; Substance P; Treatment Outcome; Vasoactive Intestinal Peptide

To explore the short and long-term efficacy of combining Fuzhengliqi mixture (FLM) with acupuncture in treating functional constipation (FC).. The 560 patients with confirmed diagnosis of FC were randomly assigned to four groups: FLM group, acupuncture group, combined therapy group, and control group. There were 140 cases in each group. The FLM group was administered FLM 60 mL twice a day, while the acupuncture group was treated with acupuncture at acupoints Tianshu (ST 25), Shangjuxu (ST 37), Zusanli (ST 36), Dachangshu (BL 25), and Zhigou (TE 6) twice a day, the combined therapy group with FLM and acupuncture, and the control group was administered mosapride (5 mg thrice a day) and Macrogol 4000 (10 g twice a day). The treatment lasted 6 weeks. The defecation interval, stool property, constipation symptoms, and accompanying symptoms were recorded, graded, and scored. The gastrointestinal transit time (GITT) and motilin (MTL) level in serum and life quality score were detected at three time points (pre-treatment, at the end of treatment, and 60 weeks post-treatment). Moreover, the adverse reactions were also observed.. In the FLM group 2 cases were eliminated for not taking medication strictly according to the research plan and 1 case was lost to follow-up, while 2 cases in the acupuncture group and 2 cases in the combined therapy group were lost to follow-up. Compared with those detected pre-treatment, the defecation interval, stool property, constipation symptom grade, accompanying symptom grade, and GITT were all decreased markedly at the end of treatment in every group, while the MTL levels in serum and life quality score were increased markedly (P < 0.01), the above-mentioned detecting indices were better in the combined therapy group than those in other groups (P < 0.05). Compared with the end of treatment, above-mentioned detecting indices all recurred significantly in the FLM group and control group 60 weeks post-treatment (P > 0.05), but these indices recurred insignificantly in the acupuncture and combined therapy groups (P > 0.05). The short and long-term total effective rates in the combined therapy group were significantly different from those in other groups (P < 0.05 or P < 0.01). No serious adverse reactions were found in four groups.. Both FLM and acupuncture can significantly shorten the defecation interval and GITT, increase MTL levels in serum, decrease the scores of stool property, constipation symptoms, and accompanying symptoms in patients with FC to increase their life quality. The combined therapy is much better in long-term efficacy and the safety is also good, worth spreading in clinical practice.

Topics: Acupuncture Points; Acupuncture Therapy; Adolescent; Adult; Aged; Constipation; Defecation; Drugs, Chinese Herbal; Female; Humans; Male; Middle Aged; Motilin; Time Factors; Treatment Outcome; Young Adult

This study explores the effects of fat-free milk supplementation on individuals with chronic constipation with regard to levels of motilin and acylated and des-acylated ghrelin (which affect intestinal motility) and compares them with data from control subjects given whole milk supplementation.. The investigation was designed according to the constipation severity test of individuals whose ages and body mass indexes were comparable. Individuals with mild constipation (n=10) were supplemented with 400 mL of fat-free milk daily; moderate constipation cases (n=10) were supplemented with 600 mL, and severe constipation cases (n=10) were supplemented with 800 mL of fat-free milk daily. Healthy control subjects were administered 400 mL of fat-free milk (group 1), which was followed a month later by administration of 400 mL of whole milk for 3 days (group 2). Blood samples were collected from the subjects before and after milk supplementation for hormone analyses. Motilin and acylated and des-acylated ghrelin were quantified with ELISA assay.. Supplementation of fat-free milk significantly increased levels of circulating motilin and ghrelin in all groups, including the control subjects, but whole milk supplementation led to a decrease in these hormone levels in the control subjects.. Drinking fat-free milk might be a new way of solving constipation.

Topics: Acylation; Adult; Aged; Animals; Biological Products; Case-Control Studies; Chronic Disease; Constipation; Dietary Fats; Dietary Supplements; Enzyme-Linked Immunosorbent Assay; Female; Gastrointestinal Motility; Ghrelin; Humans; Male; Middle Aged; Milk; Motilin; Severity of Illness Index

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

Visceral hypersensitivity is a feature of the irritable bowel syndrome (IBS). Postprandial symptoms are common in these patients. The effects of nutrients on colonic perception in IBS are incompletely understood.. We studied 13 healthy subjects and 16 patients with IBS-eight had diarrhoea predominant (IBS-D) and eight constipation predominant (IBS-C) IBS.. Colonic perception thresholds to balloon distension and viscerosomatic referral pattern were assessed before and after duodenal infusion of lipid or saline, respectively. At the end of the infusions, plasma levels of gastrointestinal peptides were determined.. Lipids lowered the thresholds for first sensation, gas, discomfort, and pain in the IBS group but only for gas in the control group. The percent reduction in thresholds for gas and pain after lipids was greater in the IBS and IBS-D groups but not in the IBS-C group compared with controls. IBS patients had an increased area of referred discomfort and pain after lipids compared with before infusion whereas the referral area remained unchanged in controls. No group differences in colonic tone or compliance were observed. In both groups higher levels of cholecystokinin, pancreatic polypeptide, peptide YY, vasoactive intestinal polypeptide, and neuropeptide Y were seen after lipids. Motilin levels were higher in patients and differences in the subgroups were observed. Levels of corticotrophin releasing factor were lower in the constipated group than in the diarrhoea group.. Postprandial symptoms in IBS patients may be explained in part by a nutrient dependent exaggerated sensory component of the gastrocolonic response.

Topics: Adult; Analysis of Variance; Case-Control Studies; Catheterization; Cholecystokinin; Colon; Colonic Diseases, Functional; Constipation; Diarrhea; Dietary Fats; Female; Humans; Male; Middle Aged; Motilin; Neuropeptide Y; Pain Threshold; Pancreatic Polypeptide; Peptide YY; Postprandial Period; Pressure; Statistics, Nonparametric; Stomach; Vasoactive Intestinal Peptide

Abnormalities of hormones affecting gastrointestinal motility have been found in "functional" disorders of the gastrointestinal system in adults. One such disorder of childhood, encopresis, is frequently associated with constipation, the treatment of which often eliminates the soiling. We hypothesized that hormones affecting gastrointestinal motility were different between encopretic patients and matched controls.. Ten encopretic patients were matched by age, race, and sex with controls who had no history of encopresis or constipation. After an overnight fast, each child consumed a meal of Ensure, the amount of which was based on body weight. Plasma levels of gastrin, pancreatic polypeptide, cholecystokinin, motilin, thyroxine, estrogen, and insulin were measured 20 and 5 minutes before the meal, and 5, 10, 15, 30, 45, 60, 90, 120, 150, and 180 minutes after the meal.. Postprandial levels of pancreatic polypeptide remained consistently higher and peaked earlier (P < .05) for encopretic patients. The motilin response was lower (P < .03) for encopretic children than for controls.. We conclude that pancreatic polypeptide and motilin responses to a meal are different in encopretic children than in children in the control group. These gastrointestinal hormone findings may in part explain and/or be the result of the severe constipation that frequently underlies the fecal soiling found in these patients. These findings also suggest the motility of the stomach and small intestine may be abnormal in encopresis.

Topics: Adolescent; Child; Constipation; Eating; Encopresis; Female; Humans; Male; Motilin; Pancreatic Polypeptide

Functional constipation is the most common form of constipation, and its exact aetiology is still unclear. However, it is known that deficiencies in hormonal factors cause constipation by changing physiological mechanisms. Motilin, ghrelin, serotonin acetylcholine, nitric oxide, and vasoactive intestinal polypeptide are factors that play a role in colon motility. There are a limited number of studies in the literature where hormone levels and gene polymorphisms of serotonin and motilin are examined. Our study aimed to investigate the role of motilin, ghrelin, and serotonin gene/receptor/transporter polymorphisms in constipation pathogenesis in patients diagnosed with functional constipation according to the Rome 4 criteria.. Sociodemographic data, symptom duration, accompanying findings, the presence of constipation in the family, Rome 4 criteria, and clinical findings according to Bristol scale of 200 cases (100 constipated patients and 100 healthy control) who applied to Istanbul Haseki Training and Research Hospital, Pediatric Gastroenterology Outpatient Clinic, between March and September 2019 (6-month period) were recorded. Polymorphisms of motilin-MLN (rs2281820), serotonin receptor-HTR3A (rs1062613), serotonin transporter-5-HTT (rs1042173), ghrelin-GHRL (rs27647), and ghrelin receptor-GHSR (rs572169) were detected by real-time PCR.. There was no difference between the two groups in terms of sociodemographic characteristics. Notably, 40% of the constipated group had a family history of constipation. The number of patients who started to have constipation under 24 months was 78, and the number of patients who started to have constipation after 24 months was 22. There was no significant difference between constipation and control groups in terms of genotype and allele frequencies in MLN, HTR3A, 5-HTT, GHRL, and GHSR polymorphisms (p<0.05). Considering only the constipated group, the rates of gene polymorphism were similar among those with/without a positive family history of constipation, constipation onset age, those with/without fissures, those with/without skin tag, and those with type 1/type 2 stool types according to the Bristol stool scale.. Our study results showed that gene polymorphisms of these three hormones may not be related to constipation in children.

Topics: Child; Constipation; Ghrelin; Humans; Motilin; Polymorphism, Genetic; Serotonin

In this study, we aimed to investigate the role of circORC2 in modulating miR-19a and its downstream signalling during the pathogenesis of STC. In this study, three groups of patients, that is healthy control (HC) group, normal transit constipation (NTC) group (N = 42) and slow transit constipation (STC) group, were, respectively, recruited. RT-PCR and Western blot analysis were exploited to investigate the changes in the expression levels of miR-19a and circORC2 in these patients, so as to establish a circORC2/miR-19a signalling pathway. The basic information of the patients showed no significant differences among different patient groups. Compared with the HC group, concentrations of neurotensin (NST) and motilin (MLN) were both significantly reduced in the NTC and STC groups, especially in the STC group. Also, miR-19a level was highest, whereas circORC2 level was lowest in the STC group. Furthermore, circORC2 was validated to sponge the expression of miR-19a, and the transfection of circORC2 reduced the expression of miR-19a. Meanwhile, MLN and NST mRNAs were both targeted by miR-19a, and the transfection of circORC2 dramatically up-regulated the expression of MLN and NST. On the contrary, the transfection of circORC2 siRNA into SMCs and VSMCs exhibited the opposite effect of circORC2. Collectively, the results of this study established a regulatory relationship among circORC2, miR-19a and neurotensin/motilin, which indicated that the overexpression of circORC2 could up-regulate the levels of neurotensin and motilin, thus exerting a beneficial effect during the treatment of STC.

Topics: Aged; Apoptosis; Biomarkers; Case-Control Studies; Cell Proliferation; Cells, Cultured; Constipation; Female; Gene Expression Regulation; Humans; Male; MicroRNAs; Motilin; Neurotensin; Origin Recognition Complex; Prognosis; RNA, Circular

Functional constipation is an important clinical problem among chidren all over the world. Its main cause is not completely understood. Motilin is a gastrointestinal hormone that increases intestinal motility. In this study, we aimed to investigate the serum motilin levels and its relationship with stool consistency and motilin gene polymorphisms in constipated children.. In this study we investigated 91 constipated patients (mean age 6.84±3.55 years) and 100 healthy controls (mean age 7.78±4.25 years). Serum motilin levels were assessed by sandwich enzyme-linked immunosorbent assay. rs2281820 (c.44 C>T) and rs2281818 (c.66 C>T) mutations were evaluated for motilin gene polymorphisms.. Serum motilin levels were significantly lower in constipated children than healthy controls (6.20±7.86 vs. 11.54±17.89 pg/mL, respectively, P=0.008). Serum motilin levels were significantly correlated with Bristol stool scale rate (r=0.193, P=0.011) in whole study group, but in the constipation group there was no significant correlation (r=-0.072, P=0.528). There were no differences in terms of presence or distribution of the polymorphisms of rs2281820 (c.44 C>T) and rs2281818 (c.66 C>T) in both groups. There was not a significant difference between different polymorphism groups regarding serum motilin concentrations in whole study group and also in both of the study groups.. This study indicated for the first time that serum motilin levels decreased in constipated children. Further studies are needed to clarify whether motilin or motilin gene polymorphisms has a role in pathogenesis of functional constipation.

Topics: Child; Child, Preschool; Constipation; Gastrointestinal Motility; Humans; Motilin; Polymorphism, Genetic

Constipation is a prevalent and burdensome gastrointestinal (GI) disorder that seriously affects the quality of human life. This study evaluated the effects of the P. pentosaceus B49 (from human colostrum) on loperamide (Lop)-induced constipation in mice. Mice were given P. pentosaceus B49 (5 × 109 CFU or 5 × 1010 CFU) by gavage daily for 14 days. The result shows that P. pentosaceus B49 treatment relieved constipation in mice by shortening the defecation time, increasing the GI transit rate and stool production. Compared with the constipation control group, the P. pentosaceus B49-treated groups showed decreased serum levels of inhibitory neurotransmitters (vasoactive intestinal peptide and nitric oxide), increased serum levels of excitatory neurotransmitters (acetylcholinesterase, motilin, and gastrin), and elevated cecal concentration of short chain fatty acids (SCFAs). Analysis of cecal microbiota reveals that P. pentosaceus B49 was colonized in the intestine of constipated mice, and altered the cecal microbiota by increasing beneficial SCFAs-producing bacteria (i.e., Lactobacillus, Ruminococcaceae_UCG-014, and Bacteroidales_S24-7) and decreasing potential pathogenic bacteria (i.e., Staphylococcus and Helicobacter). Moreover, transcriptome analysis of the colon tissue shows that P. pentosaceus B49 partly normalized the expression of genes related to GI peristalsis (i.e., Ache, Chrm2, Slc18a3, Grp, and Vip), water and electrolyte absorption and transport (i.e., Aqp4, Aqp8, and Atp12a), while down-regulating the expression of pro-inflammatory and pro-oncogenic genes (i.e., Lbp, Lgals2, Bcl2, Bcl2l15, Gsdmc2, and Olfm4) in constipated mice. Our findings indicate that P. pentosaceus B49 effectively relieves constipation in mice and is a promising candidate for treating constipation.

Topics: Acetylcholinesterase; Animals; Bacteria; Colon; Colostrum; Constipation; Fatty Acids, Volatile; Feces; Gastrins; Gastrointestinal Transit; Hormones; Humans; Intestines; Loperamide; Male; Mice; Mice, Inbred BALB C; Milk, Human; Motilin; Neurotransmitter Agents; Oxidative Stress; Pediococcus pentosaceus; Peristalsis; Probiotics; RNA, Ribosomal, 16S; Transcriptome

Constipation is a common affliction which causes discomfort and affects the quality of life of affected individuals. Naringenin (NAR), a natural flavonoid widely found in citrus fruits and tomatoes, has been reported to exhibit various pharmacological effects, such as anti-inflammatory, anti-atherogenic, anti-mutagenic, hepatoprotective and anticancer effects. Increasing evidence has indicated that NAR has potential for use in the treatment of constipation. Thus, the aim of this study was to evaluate the laxative effects of NAR in mice with loperamide-induced (Lop-induced) constipation. The data indicated that NAR relieved Lop-induced constipation in mice based on the changes of fecal parameters (numbers, weight and water content), the intestinal charcoal transit ratio and the histological alteration. ELISA revealed that NAR regulated the production levels of gastrointestinal metabolic components, such as motilin (MTL), gastrin (Gas), endothelin (ET), substance P (SP), acetylcholinesterase (AChE) and vasoactive intestinal peptide (VIP) in serum. The expression levels of enteric nerve-related factors, glial cell line-derived neurotrophic factor (GDNF), transient receptor potential vanilloid 1 (TRPV1), nitric oxide synthase (NOS), c-Kit, stem cell factor (SCF) and aquaporin 3 (AQP3) were examined by western blot analysis and RT-PCR analysis. The results of this study suggest that NAR relieves Lop-induced constipation by increasing the levels of interstitial cells of Cajal markers (c-Kit and SCF), as well as AQP3. Thus, NAR may be effective as a candidate in patients suffering from lifestyle-induced constipation.

Topics: Animals; Aquaporin 3; Constipation; Endothelins; Flavanones; Gastrins; Gastrointestinal Tract; Gene Expression Regulation; Humans; Interstitial Cells of Cajal; Laxatives; Loperamide; Mice; Motilin; Proto-Oncogene Proteins c-kit; Stem Cell Factor

This study was to probe the effects of bacterial cellulose (BC) on diphenoxylate-induced constipation in rats. Administration with BC at 500 mg/kg of body weight in diphenoxylate-induced constipation rats distinctly improved the carmine propulsion rate (83.5 ± 5.2%), shortened the defecating time of the first red feces (249.0 ± 23.3 min), and increased the weight of carmine red feces within 5 h (2.7 ± 1.3 g). The levels of aquaporins (AQP-2, AQP-3, and AQP-4) and inhibitory neurotransmitters (nitric oxide, nitric oxide synthetase, vasoactive intestinal peptide, and arginine vasopressin) in the BC-treated groups reduced by 31.9-40.0% ( p < 0.01) and 21.1-67.7% ( p < 0.01) compared to those in the constipation group, respectively. However, the secretion of excitability neurotransmitters (substance P and motilin) in the BC-treated groups was increased by 20.0-39.9% ( p < 0.01). The activities of ATPases in the colon of constipation rats were significantly weakened by BC administration ( p < 0.01). Histological morphology of the colon showed that BC supplementation could effectively increase the length of villus cells and the thickness of colonic mucosa and muscle ( p < 0.01). Moreover, BC supplementation could protect colonic smooth muscle cells against apoptosis. All of the findings suggest that BC supplementation effectively relieves constipation in rats and BC would be used as a great promising dietary fiber for alleviating constipation.

Topics: Acetobacteraceae; Animals; Aquaporins; Cellulose; Constipation; Defecation; Diphenoxylate; Humans; Intestinal Mucosa; Male; Motilin; Rats; Rats, Sprague-Dawley; Substance P

To investigate whether pathophysiological differences exist among healthy controls (HC) and patients with slow and normal transit constipation (STC and NTC), we evaluated (1) gastrointestinal (GI) symptoms using validated questionnaires; (2) circulating concentrations of neurotensin, motilin, corticotrophin-releasing factor (CRF), and somatostatin; and (3) possible differences in frequency distribution of the neurotensin rs1800832 A/G and Neurotensin Receptor 1 rs6090453 C/G SNPs.. Fifty-one patients with severe functional constipation and 20 HC completed the study. Symptoms were evaluated by GSRS and Constipaq scoring system. Plasma concentrations of GI peptides were evaluated by ELISA on fasting and six sequential blood samples after a standard meal. Genotyping was performed by PCR and endonuclease digestion.. Symptom profiles largely overlapped between NTC and STC patients. As for peptide profiles, neurotensin showed lower concentrations at 60 and 90 min in STC versus HC, and motilin showed throughout the curve 85% and 82% lower levels in STC than HC and NTC, respectively. Finally, neurotensin polymorphism resulted in being associated with the peptide levels.. Symptom profile is not a reliable tool to discriminate STC, whilst the GI peptide profiles might help in identifying it.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Colon; Constipation; Female; Gastrointestinal Contents; Gastrointestinal Tract; Gastrointestinal Transit; Genotype; Humans; Male; Middle Aged; Motilin; Neurotensin; Polymorphism, Single Nucleotide; Surveys and Questionnaires; Young Adult

Topics: Animals; Constipation; Dendrobium; Female; Gastrins; Gastrointestinal Transit; Humans; Laxatives; Male; Mice; Mice, Inbred ICR; Motilin; Plant Extracts; Substance P

In the present study, the therapeutic effects of Lactobacillus casei Qian (LC-Qian), the key microorganism in Tibetan yak yoghurt, on activated carbon-induced constipation were determined in vivo. ICR mice were treated with LC-Qian for nine days by oral administration. The body weight, defecation status, gastrointestinal transit and defecation time of mice were assessed, and the serum levels of motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) were further evaluated. Bisacodyl was used as the positive control. The time until the first black stool defecation following carbon intake of the normal, control, 100 mg/kg bisacodyl-treated, Lactobacillus bulgaricus (LB)-treated, LC-Qian (L)-and LC-Qian (H)-treated mice was 93, 231, 121, 194, 172 and 157 min, respectively. Following treatment with LC-Qian, the gastrointestinal transit was increased to 52.4% [LC-Qian (L)] and 65.8% [LC-Qian (H)], while that in the group treated with the common lactic acid bacteria of LB was 40.3%. The MTL, Gas, ET, AChE, SP and VIP serum levels were significantly increased and levels of SS were reduced in mice following LC-Qian treatment compared with those in the control mice (P<0.05). Reverse transcription quantitative polymerase chain reaction indicated that LC-Qian raised the c-Kit, GDNF as well as SCF mRNA expression levels and reduced the TRPV1 and NOS expression levels in tissue of the small intestine in mice. These results suggested that lactic acid bacteria prevent constipation in mice, among which LC-Qian was the most effective.

Topics: Acetylcholinesterase; Animals; Body Weight; Carbon; Constipation; Defecation; Endothelins; Female; Gastrins; Gastrointestinal Transit; Gene Expression; Glial Cell Line-Derived Neurotrophic Factor; GPI-Linked Proteins; Intestine, Small; Lacticaseibacillus casei; Mice; Mice, Inbred ICR; Motilin; Probiotics; Proto-Oncogene Proteins c-kit; Somatostatin; Substance P; TRPV Cation Channels; Vasoactive Intestinal Peptide

The aim of this study was to investigate the effects of Lactobacillus fermentum Zhao (LF-Zhao) on activated carbon-induced constipation in ICR mice. ICR mice were administered lactic acid bacteria by gavage for 9 d. Body weight, diet intake, drinking amount, stool status, gastrointestinal transit distance and stool time, in addition to motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) levels in serum were monitored to evaluate the preventive effects of LF-Zhao on constipation. Bisacodyl, a laxative drug, was used as a positive control. Times to the first black stool for normal (untreated), control (no lactic acid bacteria treatment but activated carbon treated), bisacodyl-treated and L. delbrueckii subsp. bulgaricus (LB), LF-Zhao (L) (low concentration of 1×10(8) CFU/mL)- and LF-Zhao (H) (high concentration of 1×10(9) CFU/mL)-treated mice induced by activated carbon were 90, 218, 117, 180, 169 and 156 min, respectively. Following the consumption of LB, LF-Zhao (L) and LF-Zhao (H) or the oral administration of bisacodyl, the gastrointestinal transit distances were reduced by 55.2%, 61.3%, 70.6% and 94.6%, respectively. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Zhao compared with those in the control mice (p<0.05). These results demonstrated that lactic acid bacteria demonstrate preventive effects on mouse constipation and that LF-Zhao alleviated constipation symptoms better than LB.

Topics: Acetylcholinesterase; Animals; Body Weight; Carbon; Constipation; Defecation; Endothelins; Feces; Female; Gastrins; Gastrointestinal Transit; Laxatives; Limosilactobacillus fermentum; Mice, Inbred ICR; Motilin; Somatostatin; Substance P; Vasoactive Intestinal Peptide

Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Calcitonin Gene-Related Peptide; Constipation; Female; Gastrointestinal Motility; Gastrointestinal Tract; Humans; Male; Middle Aged; Morphine; Motilin; Panax; Plant Extracts; Somatostatin; Substance P; Treatment Outcome; Vasoactive Intestinal Peptide; Young Adult; Zanthoxylum; Zingiberaceae

Topics: Animals; Constipation; Diet, Fat-Restricted; Food Preservation; Ghrelin; Hot Temperature; Humans; Lactose; Lactulose; Laxatives; Milk; Motilin

Topics: Constipation; Diabetes Mellitus; Diarrhea; Humans; Inflammatory Bowel Diseases; Motilin; Radioimmunoassay

The effects of mitemcinal (GM-611), an orally active motilin agonist, on defecation were investigated in rabbits and dogs. In normal rabbits, within 0-3 h of dosing, orally administered mitemcinal (2.5-10 mg kg(-1)) increased stool weight in a dose-dependent manner without causing loose stools. Sennoside (12-48 mg kg(-1)) also facilitated defecation within 2-9 h of oral administration, but the stools were significantly loosened. In the morphine-induced constipation model, the stool weight of morphine-treated rabbits (1 mg kg(-1)) was only 37.5% of that of untreated animals. Mitemcinal (0.5-20 mg kg(-1)) dose-dependently increased stool weight without increasing stool water content. At the highest dose of mitemcinal, stool weight recovered to 83.9% of that of untreated animals. In normal dogs, mitemcinal (0.3-3 mg kg(-1)) reduced the time to first bowel movement after oral administration without inducing diarrhoea at any dose. These results indicate that mitemcinal facilitates defecation without inducing severe diarrhoea. It is suggested that mitemcinal may be a novel therapeutic agent for constipation that enables easier control of the timing of defecation because of the early onset and short duration of its action, compared with sennoside.

Topics: Animals; Constipation; Defecation; Diarrhea; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Erythromycin; Gastrointestinal Agents; Morphine; Motilin; Rabbits; Reference Values

There is little information on the gastrointestinal motility abnormalities and autonomic neuropathy of children with gastrointestinal symptoms and type 1 diabetes mellitus (T1DM).. The authors studied 33 consecutive patients (mean age, 15.3 years; 13 males) with T1DM (median duration, 7.7 years) attending the outpatient clinic because of chronic dyspepsia (CD; n = 14), or chronic constipation (CC; n = 19), and 48 consecutive non-T1DM patients (mean age, 13.7 years; 18 males), who presented with similar symptoms (18 with CD; 30 with CC). Fasting serum motilin concentrations and cardiovascular autonomic function tests (CAFT) were assessed and compared with those of age- and gender-matched healthy control subjects. Gastric emptying half time (GE t1/2) of a solid meal and mouth-to-anus transit time (MATT) were measured in patients with CD and CC, respectively.. CAFT was comparable between patients with T1DM and healthy control subjects. GE t1/2 and MATT were not different between T1DM patients and non-T1DM patients with CD and CC, respectively. However, a marginally significant positive correlation was found in the patients with T1DM between GE t1/2 and blood glucose concentrations (R = 0.54; P = 0.08). In addition, serum motilin concentrations were significantly lower in patients with T1DM compared with healthy control subjects (P < 0.0005), and in patients with T1DM and higher serum glucose concentrations compared with those with lower serum glucose concentrations (P = 0.03).. Autonomic neuropathy is not an etiological factor of gastrointestinal symptoms in children and adolescents with diabetes. Mild or moderate hyperglycemia does not affect gastrointestinal motility.

Topics: Adolescent; Blood Glucose; Case-Control Studies; Child; Constipation; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Dyspepsia; Female; Gastric Emptying; Gastrointestinal Motility; Gastrointestinal Transit; Humans; Hyperglycemia; Male; Motilin

Erythromycin has been shown to have profound prokinetic effects on the gastrointestinal tract of humans and animals, probably through its action on endogenous motilin receptors. The purpose of this study was to determine both the direct and indirect effects ('off contraction') of erythromycin and motilin on ex vivo circular muscle strips of the distal colon from patients with or without idiopathic chronic constipation (ICC).. Cumulative concentrations of erythromycin (1-20 microM) and motilin (0.05-1 microM) were tested in both control and ICC preparations in order to evaluate the direct drugs effect. A range doses of both erythromycin (0.5-10 microM) and motilin (0.05-0.5 microM) were tested on their ability to affect the off-contraction that follows the typical inhibitory response evoked by low frequencies of Electrical Field Stimulation (EFS) (1-5 Hz, 20 V, 1 msec pulse trains lasting 1 min).. The direct effect of both erythromycin and motilin was a slight increase (less than 10% of the maximal ACh-induced contraction) in the basal tension, with no dose-response relationship. The off-contraction, evoked by EFS, was not affected by drugs pretreament in control preparations. Conversely, in ICC preparations both drugs significantly increased the off-contraction (about 30%).. Erythromycin causes mainly an indirect contractile effect in circular muscle strips from ICC patients. This effect may be related to the activation of inhibitory neuronal motilin receptors. This activation might potentiate NANC relaxation, proportionally increasing the circumferential reflex contraction that follows the EFS-induced relaxation.

Topics: Adult; Aged; Anti-Bacterial Agents; Chronic Disease; Colon; Constipation; Erythromycin; Humans; In Vitro Techniques; Middle Aged; Motilin; Muscle Contraction; Muscle, Smooth

As abnormalities of circulating gut regulatory peptides may have pathogenetic relevance in chronic idiopathic slow-transit constipation, we measured fasting and postprandial levels of plasma pancreatic polypeptide, motilin, cholecystokinin, neurotensin, and somatostatin in women with the disease. Results were compared with those of women with normal bowel habits.. Eight women with slow-transit constipation and 10 healthy women were studied. Blood samples were taken at regular intervals in fasting conditions and for 3 h after a standard solid-liquid meal (550 kcal). Gut peptide plasma levels were measured with a radioimmunoassay.. Fasting gut peptide levels and postprandial pancreatic polypeptide responses were normal in constipated patients, in whom, however, motilin levels did not increase after the meal, and postprandial concentration-time curves of cholecystokinin, neurotensin, and somatostatin were delayed. Mean +/- standard error of the mean peak times in patients and in controls were, respectively, 99 +/- 14.7 and 46 +/- 4.1 min (P < 0.01, Mann-Whitney test) for cholecystokinin, 135 +/- 9.8 and 60 +/- 3.9 min (P < 0.01) for neurotensin, and 111 +/- 17.7 and 51 +/- 6.0 min (P < 0.05) for somatostatin.. Patients with slow-transit constipation have abnormal postprandial patterns of motilin, cholecystokinin, neurotensin, and somatostatin.

Topics: Adult; Cholecystokinin; Constipation; Fasting; Female; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Middle Aged; Motilin; Neuropeptides; Neurotensin; Pancreatic Polypeptide; Postprandial Period; Radioimmunoassay; Somatostatin; Time Factors

Topics: Cisapride; Constipation; Diarrhea; Domperidone; Dumping Syndrome; Gastric Emptying; Gastrointestinal Motility; Humans; Intestinal Diseases; Intestinal Pseudo-Obstruction; Intestine, Small; Metoclopramide; Motilin; Parasympathomimetics; Piperidines; Serotonin Antagonists; Stomach Diseases

The plasma motilin levels were studied in seven patients with severe long-standing idiopathic constipation before and after a fat-rich test meal. The results were compared with those of a control group consisting of 10 apparently healthy persons with normal bowel function. The constipated patients had reduced basal motilin levels and a reduced motilin release after the test meal. Motilin is known to stimulate intestinal motility by inducing interdigestive descending contractions in the stomach and small intestine. A defective motilin release may therefore play a part in the pathogenesis of idiopathic constipation.

Topics: Adult; Chronic Disease; Constipation; Dietary Fats; Female; Food; Gastrointestinal Motility; Humans; Middle Aged; Motilin; Radioimmunoassay

Motilin, pancreatic polypeptide and gastrin blood concentrations in response to drinking water have been studied in 40 patients with functional bowel disease and compared with results in two groups of healthy control subjects. Patients with slow transit constipation and idiopathic megacolon showed impaired motilin release. Pancreatic polypeptide release was reduced in patients with slow transit constipation, but increased in those with functional diarrhoea. Gastrin release was impaired in all groups complaining of chronic constipation. Circulating motilin, pancreatic polypeptide and gastrin concentrations appear to bear some relationship to intestinal transit time in patients with functional bowel disorders.

Topics: Adult; Colonic Diseases, Functional; Constipation; Diarrhea; Drinking; Female; Gastrins; Humans; Intestinal Diseases; Male; Megacolon; Middle Aged; Motilin; Pancreatic Polypeptide; Water