gastrins and Constipation

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: Bradykinin; Cecum; Cholecystokinin; Colitis, Ulcerative; Colon; Colonic Diseases, Functional; Constipation; Diarrhea; Diverticulum, Colon; Gastrins; Gastrointestinal Motility; Humans; Muscle Contraction; Parasympathomimetics; Prostaglandins; Radiography; Rectum; Serotonin

Chronic constipation is a common gastrointestinal condition associated with intestinal inflammation and considerably impaired quality of life, affecting about 20% of Americans. Dietary fiber and laxatives aid in its treatment but do not fully address all symptoms, such as intestinal inflammation. Mango (Mangifera indica L.), a fiber- and polyphenol-rich fruit may provide anti-inflammatory effects in constipation.. The 4 week consumption of mango fruit (300 g) or the equivalent amount of fiber is investigated in otherwise healthy human volunteers with chronic constipation who are randomly assigned to either group. Blood and fecal samples and digestive wellness questionnaires are collected at the beginning and end of the study. Results show that mango consumption significantly improve constipation status (stool frequency, consistency, and shape) and increase gastrin levels and fecal concentrations of short chain fatty acid (valeric acid) while lowering endotoxin and interleukin 6 concentrations in plasma.. In this pilot study, the consumption of mango improves symptoms and associated biomarkers of constipation beyond an equivalent amount of fiber. Larger follow-up studies would need to investigate biomarkers for intestinal inflammation in more detail.

Topics: Adolescent; Adult; Aged; Biomarkers; Constipation; Dietary Fiber; Fatty Acids, Volatile; Female; Gastrins; Humans; Inflammation; Male; Mangifera; Middle Aged; Polyphenols

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

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

This study investigates the effects of Uliveto, a bicarbonate-alkaline mineral water, in experimental models of diarrhea, constipation and colitis. Rats were allowed to drink Uliveto or oligomineral water (control) for 30 days. Diarrhea and constipation were evoked by 16,16-dimethyl-prostaglandin E(2) (dmPGE(2)) or loperamide, respectively. Colitis was induced by 2,4-dinitrobenzenesulfonic acid (DNBS) or acetic acid. Gastric emptying, small-intestinal and colonic transit were evaluated. dmPGE(2)-induced diarrhea reduced gastric emptying and increased small-intestinal and colonic transit. In this setting, Uliveto water enhanced gastric emptying, and this effect was prevented by L-365,260 (gastrin receptor antagonist). Loperamide-induced constipation reduced gastric emptying, small-intestinal and colonic transit, and these effects were prevented by Uliveto water. L-365,260 counteracted the effects of Uliveto on gastric emptying, while alosetron (serotonin 5-HT(3) receptor antagonist) blunted the effect of Uliveto on colonic transit. Gastric emptying, small-intestinal and colonic transit were reduced in DNBS-induced colitis, and Uliveto water enhanced gastric emptying and normalized small-intestinal and colonic transit. Gastric emptying, small-intestinal and colonic transit were also reduced in acetic acid-induced colitis, and Uliveto increased both gastric emptying and small-intestinal transit. In conclusion, Uliveto water exerts beneficial effects on gastrointestinal motility in the presence of bowel motor dysfunctions. The effects of Uliveto water on gastric emptying depend on gastrin-mediated mechanisms, whereas the activation of serotonergic pathways accounts for the modulation of colonic functions.

Topics: Animals; Benzodiazepinones; Bicarbonates; Colitis; Constipation; Diarrhea; Disease Models, Animal; Gastric Emptying; Gastrins; Gastrointestinal Motility; Hydrogen-Ion Concentration; Male; Mineral Waters; Phenylurea Compounds; Rats; Rats, Wistar; Receptors, Serotonin, 5-HT3

Slow transit constipation may be part of a more generalized gastrointestinal motility disorder.. Gastric motor and sensory function were evaluated using a barostat in 17 patients with slow transit constipation and in 16 healthy controls. A step-wise isobaric distension procedure was performed, followed by a barostat procedure including a liquid meal. Symptoms were scored using visual analog scales. Plasma levels of gastrointestinal hormones were determined postprandially.. Proximal gastric compliance was significantly reduced in the patients. Basal gastric volume did not differ between patients and controls. Postprandial fundus relaxation was significantly reduced in the patients and correlated significantly with daily upper gastrointestinal symptoms. Postprandial secretion of cholecystokinin and gastrin was reduced in the patients.. In patients with slow transit constipation, proximal gastric compliance is reduced and postprandial fundus relaxation is impaired. These findings support the hypothesis that slow transit constipation may be part of a pan-enteric disorder.

Topics: Adult; Aged; Case-Control Studies; Cholecystokinin; Constipation; Enteric Nervous System; Female; Gastrins; Gastrointestinal Transit; Humans; Male; Middle Aged; Perception; Pressure; Stomach

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

To determine the frequency of gastrointestinal symptoms in primary hyperparathyroidism, we retrospectively analyzed 100 consecutive patients seen at Emory University Hospital from Jan 1, 1977 through March 1, 1979. At the time of diagnosis, 28 patients complained of nausea, 19 of vomiting, 29 of abdominal pain, and 33 of constipation. One patient presented with acute pancreatitis and 14 had ulcer disease (two gastric and 12 duodenal ulcers). Hypercalcemia increases gastric acid secretion and may account for associated ulcer disease and the ulcer-like pain in primary hyperparathyroidism. The mechanisms causing the other gastrointestinal symptoms in hypercalcemia remain to be elucidated. These symptoms abate on correction of hyperparathyroidism.

Topics: Constipation; Female; Gastrins; Gastrointestinal Diseases; Humans; Hypercalcemia; Hyperparathyroidism; Male; Pancreatitis; Peptic Ulcer

Topics: Colon, Sigmoid; Constipation; Diarrhea; Electromyography; Gastrins; Gastrointestinal Motility; Humans; Pressure