vasoactive-intestinal-peptide and Constipation

Topics: Adult; Child, Preschool; Chronic Disease; Colectomy; Colon; Colostomy; Constipation; Electric Stimulation Therapy; Enema; Female; Gastrointestinal Motility; Humans; Infant; Male; Manometry; Monitoring, Ambulatory; Multiple Endocrine Neoplasia Type 2b; Neurons; Nitric Oxide Synthase; Proto-Oncogene Proteins c-kit; Substance P; Vasoactive Intestinal Peptide

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 observe the effect of vasoactive intestinal peptide (VIP) on the metabolism of intestinal fluid and cyclic AMP protein kinase A signaling pathway (cAMP-PKA) and water channel protein 3 (AQP3) in rats with constipation, and to explore the mechanism of VIP in the treatment of constipation.
 Methods: A total of 45 healthy adult rats were randomly divided into a control group, a model group, a model +VIP group. After 4 weeks of VIP treatment, the first black stool time were examined with the ink gastric method; the water content in feces was calculated; the morphological changes in colonic tissues were observed by HE staining. The expression of VIP and AQP3 protein levels in colon tissues were detected by Western blot; and the cAMP, PKA, AQP3 mRNA expression levels were detected by quantitative real time polymerase chain reaction (qPCR). 
 Results: Compared with the control group, the first black stool time was prolonged, the water content of fecal decreased significantly (both P<0.01); part of the colon mucosa epithelial cells were destructed; the goblet cell volume decreased and quantity was reduced; the contents of AQP3 and VIP in colon tissues were significantly decreased, and the cAMP, PKA and AQP3 mRNA levels were decreased in the model group (all P<0.05). Compared with the model group, the first black stool time in the model +VIP group was shortened, the fecal water content increased significantly (both P<0.05); the mucosal epithelium integrity improved, the number of goblet cells increased; the content of AQP3 and VIP in colon tissues was increased, and the cAMP, PKA, and AQP3 mRNA levels were elevated (all P<0.05).
 Conclusion: Intravenous injection of VIP can regulate intestinal fluid metabolism and improve the symptoms of constipation in rats, which might be related to the regulation of VIP-cAMP-PKA-AQP3 signaling pathway.. 目的：观察血管活性肠肽(vasoactive intestinal peptide，VIP)对便秘大鼠肠道水液代谢、环磷酸腺苷-蛋白激酶A信号通路(cyclic AMP protein kinase A signaling pathway，cAMP-PKA)和水通道蛋白3(water channel protein 3，AQP3)的影响，探讨VIP治疗便秘的作用及机制。方法：45只健康成年Sprague-Dawley大鼠随机分为空白对照组、模型组、模型+
VIP组。给药4周后，墨汁灌胃法检测大鼠首粒黑便排出时间；根据大鼠粪便干湿重计算粪便含水率；HE染色观察各组大鼠结肠组织形态学变化；Western 印迹检测各组大鼠结肠组织中 VIP和AQP3蛋白表达水平；定量即时聚合酶链锁反应(quantitative real time polymerase chain reaction，qPCR)检测各组大鼠结肠组织中cAMP，PKA和AQP3 mRNA的表达水平。结果：与空白对照组比较，模型组大鼠首粒黑便出现时间延长，粪便含水率明显减少(均P<0.01)；结肠黏膜上皮部分破坏，杯状细胞体积减小，数量明显减少；结肠组织中VIP和AQP3蛋白含量明显减少，AQP3，cAMP和PKA mRNA相对表达水平均有所降低(均P<0.05)。与模型组比较，模型+VIP组大鼠首粒黑便出现时间缩短，粪便含水率明显增加(均P<0.05)；结肠黏膜上皮完整性明显改善，杯状细胞体积增大，数量增多；结肠组织中VIP和 AQP3蛋白含量增多，CAMP，PKA和AQP3 mRNA相对表达水平升高(均P<0.05)。结论：VIP静脉注射能够调节肠道水液代谢，改善大鼠便秘症状，其机制可能与调节VIP-cAMP-PKA-AQP3信号通路有关。.

Topics: Animals; Aquaporin 3; Aquaporins; Blotting, Western; Colon; Constipation; Cyclic AMP; Defecation; Epithelial Cells; Feces; Goblet Cells; Intestinal Mucosa; Rats; RNA, Messenger; Signal Transduction; Vasoactive Intestinal Peptide

Functional constipation (FC) is a common functional bowel disorder disease that affects life quality of a large number of people. This study aimed to explore the impact of different intensities of electro-acupuncture (EA) treatment for FC patients. Totally, 111 patients with FC meeting the Rome III criteria were randomly assigned to different intensities of EA groups (low and high intensity of EA groups) and medicine-controlled (MC) group. In EA groups, patients were treated with EA at quchi (LI11) and shangjuxu (ST37) bilaterally for 4 weeks, 5 times/week in the first 2 weeks, and 3 times/week in the last 2 weeks. In MC group, 5 mg mosapride citrate was administered orally 3 times/day for 4 weeks. Spontaneous bowel movement frequency each day was recorded using a constipation diary. Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to assess the patients' psychological state. Cortisol (CORT), substance P (SP), and vasoactive intestinal polypeptide (VIP) were evaluated at baseline and at the end of 4 weeks after treatment. As compared with the baseline, there was statistically significant increase in stool frequency every week (P<0.01), but there was no statistically significant difference among the three groups. As compared with the baseline, after 4 weeks of EA therapy, the scores of SDS and serum levels of CORT were decreased significantly in low intensity of EA group (P<0.01), and the serum levels of SP and VIP were increased significantly (P<0.05); the scores of SAS and SDS and serum levels of CORT were decreased significantly in high intensity of EA group (P<0.05), and the serum levels of SP and VIP were increased significantly (P<0.05); the serum levels of CORT and VIP were increased significantly in MC group (P<0.05). As compared with MC group, after 4 weeks of treatment, the serum levels of SP were signifcicantly increased in low intensity of EA group (P<0.01). Low and high intensities of EA could increase the stool frequency, improve the FC patient's anxiety and depression, reduce the serum levels of CORT, and increase the serum levels of SP and VIP effectively. It is concluded that both low and high intensities of EA are effective for FC patients, but there is no significant difference between the low and high intensities of EA.

Topics: Acupuncture Points; Adolescent; Adult; Analysis of Variance; Anxiety; Constipation; Defecation; Depression; Electroacupuncture; Female; Humans; Hydrocortisone; Male; Middle Aged; Outcome Assessment, Health Care; Substance P; Time Factors; Treatment Outcome; Vasoactive Intestinal Peptide; Young Adult

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

Tissue specimens from the large bowel of 18 patients with long-standing slow transit constipation were investigated to determine the distribution and density of several neuropeptides and amines in the enteric nerve system, and also of endocrine cells in comparison to normal individuals. CGRP (calcitonin gene-related peptide), galanin, glucagon, GRP (gastrin-releasing peptide), metenkephalin, motilin, neuropeptide Y (NPY), PACAP, peptide YY (PYY), serotonin, somatostatin, substance P and VIP were studied by immunohistochemistry. Tissue concentrations of VIP, substance P and galanin were also measured by radioimmunoassay. Significantly increased VIP, SP and galanin contents were found in specimens from the ascending colon. Levels of VIP and galanin were also increased in the transverse colon. Immunohistochemistry revealed only marginal changes with an increased density of PACAP nerve fibres in the smooth muscle and of VIP and PACAP nerves in the myenteric plexus of the transverse colon. In the descending colon substance P and NPY immunoreactivity were also increased in the myenteric plexus while the density of VIP nerve fibres was reduced in the mucosa/submucosa. The frequency of PYY-containing cells and the 5-HT-containing cells in the ascending colon was significantly increased in the constipated patients.

Topics: Adult; Aged; Colon; Constipation; Endocrine Glands; Female; Galanin; Gastrointestinal Transit; Humans; Immunohistochemistry; Male; Middle Aged; Neuropeptides; Radioimmunoassay; Substance P; Vasoactive Intestinal Peptide

Although Ligilactobacillus salivarius Li01 (Li01) has shown much promise in preventing multiple gastrointestinal diseases, the potential of the probiotic in alleviating constipation and the related mechanisms remain unclear. In this study, the effects of Li01 were evaluated in a loperamide-induced constipation mouse model. The results demonstrated that Li01 intervention can relieve constipation symptoms by improving water content, quantity, and morphology of feces and act as an intestinal barrier structure protector. Furthermore, Li01 can modulate gut motility (gastrointestinal transit rate), the fluid transit-associated expression of aquaporins, and the serum parameters vasoactive intestinal peptide, substance P, and somatostatin. Constipation significantly increased the levels of 5-hydroxytryotamine (5-HT) in serum (p < 0.01) and decreased the levels in the intestine (p < 0.001). Due to its function of elevating the expression of tryptophan hydroxylase 1, this was reversed after Li01 treatment. Li01 also promoted the expression of 5-HT receptor 3 and 4, indicating that the 5-HT signaling pathway may play a critical role in the mechanism by which Li01 alleviate constipation symptoms. Additionally, Li01 significantly altered the gut microbiota composition by enhancing the ratio of Firmicutes/Bacteroidetes and increasing the abundance of Rikenellaceae_RC9 genera. Based on the above results, Li01 may have the potential to effectively alleviate constipation by regulating the 5-HT pathway and alteration of the gut microbiota.

Topics: Animals; Aquaporins; Constipation; Ligilactobacillus salivarius; Loperamide; Mice; Serotonin; Signal Transduction; Somatostatin; Substance P; Tryptophan Hydroxylase; Vasoactive Intestinal Peptide

The naturally fermented yak yogurt of pastoralists in the Tibetan Plateau, China, because of its unique geographical environment and the unique lifestyle of Tibetan pastoralists, is very different from other kinds of sour milk, and the microorganisms it contains are special.. Constipation was induced in ICR mice with diphenoxylate, and the constipated mice were treated with LLSL-HFY14. The weight and feces of the mice were visually detected. Colonic tissues were observed on hematoxylin and eosin-stained sections. Serum indices were detected with kits. mRNA expression in the colon was determined by quantitative polymerase chain reaction assay.. Constipation caused weight loss, the number of defecation granules, defecation weight, fecal water content decreased, and the first black stool excretion time increased. LLSL-HFY14 alleviated these symptoms, and the effects were similar to those of lactulose (drug). The pathological examination revealed that constipation caused pathological changes in the colon, and LLSL-HFY14 effectively alleviated the disease. LLSL-HFY14 increased serum levels of motilin, gastrin, endothelin, substance P, acetylcholinesterase, and vasoactive intestinal peptide (VIP) and decreased serum levels of somatostatin in constipated mice. In addition, LLSL-HFY14 upregulated VIP, cAMP, protein kinase A, and aquaporin 3 expression in colonic tissues of constipated mice in a dose-dependent manner.. LLSL-HFY14 inhibited constipation, similar to lactulose, and has the potential to become a biological agent.

Topics: Animals; Aquaporin 3; Cattle; Constipation; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Diphenoxylate; Disease Models, Animal; Female; Lactococcus lactis; Mice; Mice, Inbred ICR; Probiotics; Signal Transduction; Somatostatin; Vasoactive Intestinal Peptide; Yogurt

BACKGROUND The aim of this study was to evaluate the effects of a new type of dietary fiber - high specific volume polysaccharide (HSVP) - on fecal properties, serum vasoactive intestinal peptide (VIP) concentration, intestinal flora count, and expression of the VIP-cAMP-PKA-AQP3 signaling pathway. MATERIAL AND METHODS Compound diphenoxylate was used in 48 healthy Wistar rats to establish a constipation model. Rats were divided into a normal control group, a constipation model group, an HSVP low-dose group, an HSVP medium-dose group, an HSVP high-dose group, and a fructose control group. We used colony count method, ELISA, WB, and RT-PCR to determine fecal moisture content, fecal hardness, fecal passage time, serum VIP concentration, number of intestinal bacteria, and VIP-cAMP-PKA-AQP3 signal pathway protein expression. RESULTS The constipation model was established successfully. HSVP (the medium dose was 10% and the high dose was 15%) improved fecal moisture content, reduced hardness, shortened fecal emptying time, increased intestinal bacteria, reduced serum VIP concentration, downregulated cAMP and PKAm RNA transcription, reduced protein expression, and reduced intestinal AQP3 expression. CONCLUSIONS HSVP improved constipation, increased the number of intestinal bacteria, and elevated expression of the VIP-cAMP-PKA-AQP3 signaling pathway. The mechanism of HSVP in regulating intestinal water metabolism in constipated rats may occur through the VIP-cAMP-PKA-AQP3 signaling pathway, and be closely related to changes in intestinal bacteria. The important role of the brain-gut-microbiome axis in the pathogenesis of constipation has been confirmed in this study.

Topics: Animals; Aquaporin 3; Constipation; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Dietary Fiber; Feces; Gastrointestinal Microbiome; Gastrointestinal Transit; Hardness; Humidity; Intestines; Polysaccharides; Rats, Wistar; RNA, Messenger; Transcription, Genetic; Treatment Outcome; Vasoactive Intestinal Peptide; Water

To compare the effects of filiform needling, electroacupuncture, and moxibustion on functional constipation in rats, and to explore the possible mechanism of these three different methods.. Male SD rats were randomly divided into blank control group (. Compared with the blank control group, the first defecation time was prolonged, and the NO, NOS and VIP contents in plasma were increased in the model group (. All the three different kinds of acupuncture and moxibustion methods have positively regulatory effect on functional constipation; electroacupuncture is the best for the regulation of plasma NO, NOS and VIP contents, while moxibustion is the best for the regulation of VIP expression in colonic tissue.

Topics: Acupuncture Points; Acupuncture Therapy; Animals; Colon; Constipation; Defecation; Humans; Male; Moxibustion; Nitric Oxide; Nitric Oxide Synthase; Rats; Rats, Sprague-Dawley; Vasoactive Intestinal Peptide

Chronic constipation (CC) is a common and severe gastrointestinal complaint in Parkinson's disease (PD), but its pathogenesis remains poorly understood. This study evaluated functionally distinct submucosal neurons in relation to colonic motility and anorectal function in PD patients with constipation (PD/CC) vs both CC and controls.. Twenty-nine PD/CC and 10 Rome III-defined CC patients were enrolled. Twenty asymptomatic age-sex matched subjects served as controls. Colonic transit time measurement and conventional anorectal manometry were evaluated in PD/CC and CC patients. Colonoscopy was performed in all three groups. Colonic submucosal whole mounts from PD/CC, CC, and controls were processed for immunohistochemistry with antibodies for vasoactive intestinal polypeptide (VIP) and peripheral choline acetyltransferase, markers for functionally distinct submucosal neurons. The mRNA expression of VIP and its receptors were also assessed.. Four subgroups of PD/CC patients were identified: delayed colonic transit plus altered anorectal manometry (65%); delayed colonic transit (13%); altered manometric pattern (13%); and no transit and manometric impairment (9%). There were no differences in the number of neurons/ganglion between PD/CC vs CC or vs controls. A reduced number of submucosal neurons containing VIP immunoreactivity was found in PD/CC vs controls (P<.05). VIP, VIPR1, and VIPR2 mRNA expression was significantly reduced in PD/CC vs CC and controls (P<.05).. Colonic motor and rectal sensory functions are impaired in most PD/CC patients. These abnormalities are associated with a decreased VIP expression in submucosal neurons. Both sensory-motor abnormalities and neurally mediated motor and secretory mechanisms are likely to contribute to PD/CC pathophysiology.

Topics: Adult; Aged; Aged, 80 and over; Cholinergic Neurons; Chronic Disease; Constipation; Down-Regulation; Female; Gastrointestinal Transit; Humans; Male; Manometry; Middle Aged; Neurons; Parkinson Disease; Rectal Diseases; RNA, Messenger; Submucous Plexus; Vasoactive Intestinal Peptide

Using an atropine-diphenoxylate-induced slow transit constipation (STC) model, this study explored the effects of the total glucosides of paeony (TGP) in the treatment of STC and the possible mechanisms.. A prospective experimental animal study.. The constipation model was set up in rats with an oral gavage of atropine-diphenoxylate and then treated with the TGP. The volume and moisture content of the faeces were observed and the intestinal kinetic power was evaluated. Meanwhile, the colorimetric method and enzyme linked immunosorbent assay (ELISA) were employed to determine the changes of nitric oxide (NO), nitric oxide synthase (NOS), vasoative intestinal peptide (VIP) and the P substance (SP) in the serum, respectively. The protein expressions of c-kit and stem cell factor (SCF) were assessed by immunohistochemical analysis and western blot, respectively, and the mRNA level of c-kit was measured by a reverse transcription polymerase chain reaction (RT-PCR).. The TGP attenuated STC responses in terms of an increase in the fecal volume and moisture content, an enhancement of intestinal transit rate and the reduction of NO, NOS and VIP in the serum. In addition, the c-kit, a labeling of interstitial cells of Cajal (ICC) increased at both protein and mRNA levels. SCF, which serves as a ligand of c-kit also increased at protein level.. The analysis of our data indicated that the TGP could obviously attenuate STC through improving the function of ICC and blocking the inhibitory neurotransmitters such as NO, NOS and VIP.

Topics: Animals; Constipation; Disease Models, Animal; Female; Gastrointestinal Motility; Glucosides; Interstitial Cells of Cajal; Neurotransmitter Agents; Nitric Oxide; Nitric Oxide Synthase; Paeonia; Prospective Studies; Proto-Oncogene Proteins c-kit; Rats; Rats, Wistar; Stem Cell Factor; Substance P; Vasoactive Intestinal Peptide

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

The slow transit time of the colon in females with constipation is due to impairment of agonist-induced contraction. The impairment is associated with downregulation of G proteins that mediate contraction and upregulation of Gs proteins that mediate relaxation. These changes are caused by overexpression of progesterone (P4) receptors in the colon, rendering its muscle cells sensitive to physiological P4 concentrations. Downregulation of Gq/11 is mediated by P4 receptor B (PR-B). We examined whether upregulation of Gs proteins increased the inhibition of contraction and whether the increase is mediated by the P4 receptor A (PR-A). These studies were conducted in colon-isolated colon muscle cells from human control and slow-transit constipation (STC) females and from guinea pigs. Muscle cell contraction was induced by CCK-8. Inhibition of contraction was induced by vasoactive intestinal polypeptide (VIP), and 8'bromo-c'AMP (8B-c'AMP) G protein levels were determined by Western blot. VIP-induced inhibition of contraction was greater in muscle cells from STC and P4-treated muscle cells. There were no differences in the inhibition induced by 8B-c'AMP between muscle cells from STC and P4-treated controls. The increased VIP-induced inhibition of muscle cells treated with P4 was blocked by pretreatment with PR-A antibodies and unaffected by PR-B antibodies. These antibodies had no effect on 8B-c'AMP induced-inhibition. The P4 upregulation of Gs proteins was blocked by PR-A antibodies and unaffected by PR-B antibodies. Similar results were obtained in muscle cells from guinea pig colons. We concluded that P4 upregulation of Gs proteins increases VIP-induced inhibition of contraction mediated by PR-A.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Adult; Animals; Antibodies; Cells, Cultured; Colon; Constipation; Cyclic AMP; Female; GTP-Binding Protein alpha Subunits, Gq-G11; GTP-Binding Proteins; Guinea Pigs; Humans; Male; Middle Aged; Muscle Contraction; Myocytes, Smooth Muscle; Progesterone; Receptors, Progesterone; Sincalide; Vasoactive Intestinal Peptide

Slow-transit constipation (STC) is recognized in children but the etiology is unknown. Abnormalities in substance P (SP), vasoactive intestinal peptide (VIP) and nitric oxide (NO) have been implicated. The density of nerve fibers in circular muscle containing these transmitters was examined in colon from children with STC and compared to other pediatric and adult samples.. Fluorescence immunohistochemistry using antibodies to NO synthase (NOS), VIP and SP was performed on colonic biopsies (transverse and sigmoid colon) from 33 adults with colorectal cancer, 11 children with normal colonic transit and anorectal retention (NAR) and 51 with chronic constipation and slow motility in the proximal colon (STC). The percentage area of nerve fibers in circular muscle containing each transmitter was quantified in confocal images.. In colon circular muscle, the percentage area of nerve fibers containing NOS > VIP > SP (6 : 2 : 1). Pediatric groups had a higher density of nerve fibers than adults. In pediatric samples, there were no regional differences in NOS and VIP, while SP nerve fiber density was higher in sigmoid than proximal colon. STC children had lower SP and VIP nerve fiber density in the proximal colon than NAR children. Twenty-three percent of STC children had low SP nerve fiber density.. There are age-related reductions in nerve fiber density in human colon circular muscle. NOS and VIP do not show regional variations, while SP nerve fiber density is higher in distal colon. 1/3 of pediatric STC patients have low SP or VIP nerve fiber density in proximal colon.

Topics: Adolescent; Adult; Age Factors; Animals; Biopsy; Child; Child, Preschool; Colon, Sigmoid; Colon, Transverse; Constipation; Female; Gastrointestinal Motility; Humans; Immunohistochemistry; Male; Nitric Oxide; Nitric Oxide Synthase; Substance P; Vasoactive Intestinal Peptide

To evaluate the roles of enteric nervous system neurotransmitters, nitric oxide (NO), substance P (SP) and vasoactive intestinal polypeptide (VIP), and interstitial cells of Cajal (ICC) in the colon in slow transit constipation in rats.. Thirty-two healthy Wistar rats were randomly assigned to control and constipated groups. In the constipated group, the rats were daily administered with diphenoxylate (8 mg/kg) to develop slow transit constipation, while the control rats were fed with water. The number and the weight of fecal granule and the body weight of rats were recorded every 5 days for 90 days. Transit functions of intestinal movement were examined by an activated charcoal suspension pushing test one week after stopping the administration of diphenoxylate. The levels of NO and SP in the colonic mucosa were measured by nitrate reductase methods and ELISA respectively. The distribution of VIP and ICC positive cells confirmed with symbolic c-kit+ cells in the colonic wall were observed by immunohistochemical methods.. The daily number of fecal granule in the constipated group was significantly less than that in the control group (P<0.01). The mean weight of each fecal granule in the constipated group was significantly higher than that in the control group (P<0.01). The discharge time of the first granule of black faeces in the constipated group (430.2+/- 132.1 min) was significantly longer than that in the control group (337.2+/- 74.7 min; P<0.05). There were no significant differences in NO and SP levels and the density of VIP positive cells in the distal colonic segment between the two groups. The number of c-kit+ cells in the distal colonic wall in the constipated group was significantly reduced compared with that in the control group (P<0.05).. The reduction of ICC number in the distal colon may be contributed to the pathogenesis of slow transit constipation in rats.

Topics: Animals; Body Weight; Coiled Bodies; Colon; Constipation; Male; Neurotransmitter Agents; Nitric Oxide; Proto-Oncogene Proteins c-kit; Rats; Rats, Wistar; Substance P; Vasoactive Intestinal Peptide

Slow transit constipation (STC) affects up to 3% of all children and is an increasingly recognized cause of chronic constipation in children. We conducted a pilot study to investigate whether genes encoding neurotransmitters (TAC1, TAC3, VIP, NOS1) and receptors (TACR1, TACR2, TACR3, KIT) could be responsible for STC.. One hundred seventeen tag single nucleotide polymorphisms (SNPs), distributed among the candidate genes, were selected from HapMap data and genotyped using Sequenom (San Diego, CA) technology in 35 affected families. Evaluation of association was performed by transmission disequilibrium test and multilocus analysis.. Five SNPs (rs3771863, rs4580655, rs11722288, rs4563545, and rs3782221) in the TACR1, TACR3, KIT, and NOS1 genes were found to be potentially associated with STC, although the significance of these results does not withstand correction for multiple testing.. Our data indicate that 5 SNPs in the NOS1, TACR1, TACR3, and KIT genes could be involved in STC, especially rs3771863 in intron 1 of TACR1, which showed the highest association.

Topics: Adolescent; Child; Child, Preschool; Chronic Disease; Constipation; Enteric Nervous System; Female; Gastrointestinal Transit; Genotype; Humans; Linkage Disequilibrium; Male; Neurotransmitter Agents; Nitric Oxide Synthase Type I; Polymorphism, Single Nucleotide; Receptors, Neurotransmitter; Vasoactive Intestinal Peptide

Fecal accumulation, constipation, soiling, and incontinence are common sequelae after repair of anorectal malformations (ARMs) in children. It is believed that besides the abnormalities of sacral roots, certain inherent abnormalities of the myenteric plexuses may play an important role in the final outcome after definitive repair.. This study was conducted to investigate the distribution of neuron-specific enolase (NSE), vasoactive intestinal peptide (VIP), and substance P (SP)-100 neurotransmitters in the rectosigmoid and fistulous tract of the ethylenethiourea-treated rat with ARMs.. ARMs were induced by administering 1% ethylenethiourea (125 mg/kg) on gestational day 10, and the litter was harvested on gestational day 21 by cesarean section. Forty-eight controls and 63 with ARMs (46 high-type and 17 low-type) were recovered. Whole-mount preparations of each rectosigmoid and fistulous communication between the rectum and genitourinary tract were stained with fluorescent antibodies against NSE, VIP, and SP-100. The tissues were counterstained with Eriochrome black-T and methyl green dyes to improve the visualization of the myenteric plexuses.. The immunoreactivity of NSE, VIP, and SP-100 was markedly reduced in the rectum and fistulous tract of high-type ARMs and slightly reduced in low-type ARMs compared with controls. Intramural nerves stained by VIP and SP-100 antisera were decreased in both types of ARM, indicating that both inhibitory and excitatory motor neural elements were affected, and this may explain the distal colonic dysmotility seen postoperatively in both high and low ARMs.

Topics: Anal Canal; Animals; Constipation; Digestive System Abnormalities; Ethylenethiourea; Female; Fetus; Immunohistochemistry; Myenteric Plexus; Neurotransmitter Agents; Phosphopyruvate Hydratase; Pregnancy; Rats; Rats, Sprague-Dawley; Rectal Fistula; Rectum; Substance P; Vasoactive Intestinal Peptide

To assess the levels of gut peptides involved in gastrointestinal motor, secretory and sensory function in colonic biopsies in irritable bowel syndrome (IBS) patients and healthy controls.. We studied 34 patients with IBS and 15 subjects without gastrointestinal symptoms. The predominant bowel pattern in the IBS patients was constipation in 17 patients (IBS-C) and diarrhoea in 17 patients (IBS-D). With radioimmunoassay, the levels of vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY) and peptide YY (PYY) were analysed in biopsies from the descending colon and ascending colon obtained during colonoscopy.. The IBS patients had lower levels of PYY in the descending colon than the controls, but the levels in the ascending colon did not differ. The NPY levels were lower in IBS-D than in IBS-C, both in the ascending colon and in the descending colon. Low levels of VIP were more common in IBS patients, but mean levels did not differ between groups. No group differences were observed for substance P. The levels of VIP, substance P and NPY were higher in the ascending colon than in the descending colon, whereas the opposite pattern was seen for PYY.. IBS patients demonstrate lower levels of PYY in the descending colon than controls. Colonic NPY levels differ between IBS subgroups based on the predominant bowel pattern. These findings may reflect the pathophysiology of IBS and the symptom variation within the IBS population.

Topics: Adult; Aged; Biopsy; Case-Control Studies; Colon; Colonic Diseases, Functional; Constipation; Diarrhea; Female; Humans; Male; Middle Aged; Neuropeptide Y; Peptide YY; Substance P; Vasoactive Intestinal Peptide

A paraneoplastic syndrome is occasionally the first clinical symptom seen with tumours. We report on two children who initially presented with paraneoplastic syndromes due to ganglioneuroblastomas: the first with severe watery diarrhoea caused by a ganglioneuroma producing vasoactive intestinal peptide, the second with non-treatable constipation, caused by ganglioneuroma-produced anti-neuronal nuclear antibodies.. Either severe diarrhoea or chronic constipation may represent rare paraneoplastic syndromes in ganglioneuroblastomas.

Topics: Adolescent; Adrenal Gland Neoplasms; Chronic Disease; Constipation; Fatal Outcome; Female; Ganglioneuroblastoma; Humans; Infant; Paraneoplastic Syndromes; Vasoactive Intestinal Peptide; Vomiting

Severe intractable constipation in children may be associated with a reduction of substance P (SP)- containing fibers in colonic circular muscle. The aim of this study was to characterize gastrointestinal transit (GIT), anorectal manometry (ARM) and electromyographic (EMG) changes in these children.. Seromuscular laparoscopic biopsies of the colon were obtained from 35 children with severe constipation. Immunofluorescent staining for SP and vasoactive intestinal peptide (VIP) were then performed on these specimens. The cohort of patients studied included a SP-deficient group (SPD, n = 25) who had reduced numbers of SP-immunoreactive nerve fibers. The other group consisted of patients with normal staining for both SP and VIP (SPN, n = 10). Gastrointestinal transit studies (gastric emptying, orocecal and colonic transit) suitable for analysis were available for 17 patients (SPD, n = 9 and SPN, n = 8). The colon was divided into segments and radioactivity counts in each segment were expressed as a percentage of the total colonic count at each time point (6, 24, 32 and 48 h). The geometric center (GC), ARM, EMG, clinical and demographic data characteristics of both groups of patients were compared.. There were no differences in demographic data, gastric emptying, orocecal transit or geometric center of transit in the colon between the two patient groups. The ARM and EMG studies suggested that the SPN group have a higher mean threshold volume of balloon distension required to initiate a rectoanal inhibitory reflex, and a higher incidence of anismus; however, this did not reach statistical significance.. These data suggest a trend that the SPN patients have a greater problem with obstructive defecation and abnormal rectal sensation than those with SPD. We were unable to confirm any defect in colonic transit in the SPD patients compared with the SPN group.

Topics: Anal Canal; Child; Child, Preschool; Colon; Constipation; Electromyography; Female; Fluorescent Antibody Technique; Gastrointestinal Transit; Humans; Infant; Male; Manometry; Retrospective Studies; Substance P; Vasoactive Intestinal Peptide

Patients suffering from idiopathic slow-transit chronic constipation have a delayed colonic transit referable to a decrease or loss of propagating contractions. Myogenic and/or neural mechanisms have been implicated in the pathophysiology of this dysfunction and neuronal abnormalities have been described at the ascending, descending and sigmoid colon. The morphology and motile behaviour of the ileocecocolonic region, which in healthy subjects regulates cecum filling and emptying, have never been investigated in such disease. Therefore, we endoscopically ascertained whether a motility impairment was present at these junctional areas and neither spontaneous nor provoked occlusive contractions were found at the cecocolonic junction. Light and electron microscope examination of the entire colon revealed apparently normal features of neurons, smooth muscle cells and interstitial cells of Cajal, while immunohistochemistry and quantitative analysis demonstrated neuronal anomalies at the junctional areas. These anomalies consisted of low total neuron density and significantly few VIP-immunoreactive neurons at the two enteric plexuses, significantly few NOS-immunoreactive neurons at the myenteric plexus and significantly more NOS-immunoreactive neurons at the submucous plexus. These findings exclude a myopathy and demonstrate the existence of a neuropathy. In particular, the presence at the ileocecocolonic region of few VIP- and NO-producing neurons suggests that there might be a reduced VIP and NO production which may result in a compromised relaxation and/or onset of propagating contractions, slowing down bolus transit. The presence at the proximal colon of such an abnormality might explain why left colectomy and/or cecorectal anastomosis are unsuccessful in patients with this disease.

Topics: Adult; Chronic Disease; Colon; Constipation; Endoscopy, Gastrointestinal; Female; Gastrointestinal Motility; Humans; Ileum; Mathematical Computing; Middle Aged; Muscle, Smooth; Neurons; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Vasoactive Intestinal Peptide

The aim of our study was to further investigate the pathophysiological mechanism underlying idiopathic chronic constipation (ICC), a disorder of colonic motility. A possible alteration of excitatory and inhibitory neurotransmission and also the role of inhibitory neurotransmitters such as nitric oxide (NO), 5'-adenosine triphosphate (ATP), and vasoactive intestinal peptide (VIP) has been evaluated on preparations of distal colon from patients with or without ICC. The isometric tension was recorded from isolated circular muscle strips of both experimental groups during pharmacological and electrical field stimulation (EFS). The contractile response obtained by acetylcholine (ACh 20 microM), EFS (20 Hz, 20 V, 1 msec, pulse trains lasting 1 min) and substance P (SP 1 microM) was significantly lower in ICC than in control preparations. The effect of inhibitory nonadrenergic, noncholinergic innervation was evaluated using EFS at low frequencies (0.5-8 Hz), after cholinergic and sympathetic blockade with atropine (3 microM) and guanethidine (3 microM). The maximum relaxation value expressed as percentage of inhibition of SP-induced contraction was significantly higher in ICC than in control preparations (87+/-2.4 and 67+/-6.3, respectively; P<0.05). Experiments with substances that antagonize or reduce the effect of putative inhibitory mediators (VIP 6-28, apamin and N(G)-nitro-L-arginine) suggest that an alteration in NO and ATP release is present in ICC preparations. In particular at a higher inhibitory frequency NO-mediated relaxation is enhanced in ICC vs control, supporting the hypothesis that excessive NO production may be involved in pathophysiological mechanism of constipation.

Topics: Acetylcholine; Adenosine Triphosphate; Adult; Atropine; Cholinergic Fibers; Chronic Disease; Colon; Constipation; Electric Stimulation; Gastrointestinal Motility; Guanethidine; Humans; In Vitro Techniques; Male; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Nitric Oxide; Substance P; Vasoactive Intestinal Peptide

After Hirschsprung's disease was ruled out for 25 children who had severe chronic constipation, the authors studied the distribution of immunoreactivity for substance P (SP) and vasoactive intestinal peptide (VIP) in the intestinal wall, using immunofluorescence. SP and VIP immunoreactivity identify excitatory and inhibitory nerve fibres, respectively. Full-thickness rectal biopsy specimens were unsatisfactory, so seromuscular biopsies of the caecum, transverse colon, and sigmoid colon were obtained (by laparoscopy and laparotomy; n = 10 patients). SP-immunoreactive fibres were markedly reduced in seven, with concomitant reduction of VIP-immunoreactive fibres in four. In two other patients, there was no obvious reduction in SP- or VIP-immunoreactive fibres. In a patient who subsequently was found to have multiple endocrine neoplasia type 2b, the myenteric plexus was markedly hyperplastic, with an increase in nerve cells and nerve fibres. VIP-immunoreactive fibres were increased, but SP-immunoreactive fibres were markedly decreased. Surgical options included proximal stoma, Malone operation, and subtotal colectomy with preservation of the rectum. Three children with subtotal colectomy have had improvement over short-term follow-up. The combination of seromuscular laparoscopic biopsies and immunofluorescence demonstration of neuropeptides may identify new variants of intestinal neuronal dysplasia than can be treated successfully with surgery.

Topics: Adenomatous Polyposis Coli; Biopsy; Child; Child, Preschool; Colectomy; Colon; Colonic Pseudo-Obstruction; Constipation; Female; Fluorescent Antibody Technique; Hirschsprung Disease; Humans; Male; Nerve Fibers; Substance P; Vasoactive Intestinal Peptide

Previous studies in patients with chronic constipation found abnormalities in the nervous tissue of the large intestine, predominantly in the muscularis externa. Since there is evidence that the nervous system of mucosa and submucosa is also involved in the control of colonic motility we investigated the contents of vasoactive intestinal polypeptide (VIP), somatostatin and substance P in rectal biopsies of patients with slow colonic transit constipation.. Twenty-two patients (17 females, 5 males) with chronic slow transit constipation (oro-anal transit with radio-opaque markers on high fibre diet > 70 h) and long-term use of laxatives, and 20 controls (12 females, 8 males) with no history of constipation, were included in this study. Large rectal biopsy specimens including the submucosa were obtained from 5 cm above the dentate line and frozen in liquid nitrogen. After microdissection of the biopsies into mucosa and submucosa the neuropeptides were extracted by boiling and homogenizing the tissue in acetic acid and determined using validated radioimmunoassays.. Patients with slow transit constipation showed, compared to healthy controls, significantly lower levels of the excitatory neurotransmitter substance P in the mucosa and submucosa of rectal biopsies. There was no difference between the two groups concerning the levels of the inhibitory neurotransmitters, VIP and somatostatin.. Slow transit constipation is associated with abnormalities of the substance P content of the enteric nervous system of mucosa and submucosa. This seems not to be related to chronic laxative use, since anthranoids cause a reduction in the levels of inhibitory neurotransmitters (VIP, somatostatin), but not of substance P, in the rat colon.

Topics: Biopsy; Case-Control Studies; Constipation; Enteric Nervous System; Female; Gastrointestinal Transit; Humans; Intestinal Mucosa; Male; Middle Aged; Radioimmunoassay; Rectum; Somatostatin; Substance P; Vasoactive Intestinal Peptide

Idiopathic chronic constipation has been correlated to neural abnormalities that consist of a reduced number of myenteric plexus neurons and a decreased concentration of VIP-positive nerve fibers within the circular muscle. Recent studies hypothesized the involvement of nitric oxide in motility disorders of the human gut. To date, no information is available on nitric oxide involvement in idiopathic chronic constipation. The density of VIP- and nitric oxide-producing neurons was evaluated by immunocytochemistry using anti-VIP and anti-nitric oxide synthase antibodies in five patients with idiopathic chronic constipation. A low total neuron density was found at the myenteric plexus. The density of VIP-positive neurons was low while that of nitric oxide synthase-positive neurons was high at both plexuses. Our data confirm that idiopathic slow-transit chronic constipation is due to abnormal neurogenic factors. The presence of numerous nitric oxide synthase-positive neurons, all along the colon and at both plexuses, supports the hypothesis that an excessive production of nitric oxide may cause the persistent inhibition of contractions.

Topics: Adult; Cell Count; Chronic Disease; Constipation; Enteric Nervous System; Female; Humans; Immunohistochemistry; Neurons; Nitric Oxide Synthase; Vasoactive Intestinal Peptide

The authors report a case of neuronal intestinal dysplasia in a 6-year-old girl. The disease is characterized by hyperplastic ganglia throughout the large and small intestine, associated with severe constipation. To better understand the pathophysiology of this disease the authors investigated the histopathologic, ultrastructural, and immunohistochemical characteristics of the intestinal tissue in this case. The hyperganglionosis was associated with immunohistochemical findings of intact expression of the neuropeptides controlling the peristaltic reflex, through lower expression of calcitonin-gene related peptide. With the recent progress in our understanding of the neural regulation of gastrointestinal function, it may now be possible to begin to understand the complex pathophysiological mechanisms underlying gastrointestinal motility disorders.

Topics: Calcitonin Gene-Related Peptide; Child; Colon; Constipation; Female; Gastrointestinal Motility; Humans; Hyperplasia; Intestinal Diseases; Myenteric Plexus; Submucous Plexus; Substance P; Vasoactive Intestinal Peptide

The distribution in the bowel wall of vasoactive intestinal polypeptide-, neuropeptide Y-, and substance P-containing nerve cell bodies and nerve fibers has been described in human sigmoid colon by immunohistochemical examination. In patients with chronic idiopathic constipation, diverticular disease, and in controls (of tissue taken from patients with carcinoma, from a site distant from the tumor that appeared macroscopically normal), the concentrations of vasoactive intestinal polypeptide, neuropeptide Y, and substance P have been measured by immunoassay in the following preparations of sigmoid colon: mucosa, whole colonic wall with mucosa dissected away, circular muscle, and taenia coli. In idiopathic constipation, the vasoactive intestinal polypeptide content of the whole wall minus mucosa was reduced when compared with controls (P less than 0.05) but was unaltered in the mucosa, circular muscle, and taenia coli. In diverticular disease, the vasoactive intestinal polypeptide content of the mucosa and whole wall minus the mucosal layer was increased when compared with control tissue (P less than 0.05 and P less than 0.02, respectively) but was unaltered in the circular muscle and taenia coli. Substance P and neuropeptide Y levels in all layers of colonic wall were unaltered in these two diseases. The disturbances in the normal neural content of vasoactive intestinal polypeptide in the bowel wall in idiopathic constipation and diverticular disease may initiate or contribute to the functional changes seen in these disorders.

Topics: Colon, Sigmoid; Constipation; Diverticulum; Female; Humans; Immunoassay; Immunohistochemistry; Male; Middle Aged; Neuropeptide Y; Substance P; Vasoactive Intestinal Peptide

To investigate the reported association between idiopathic chronic constipation and morphologic abnormalities of enteric nerves, we measured the concentrations of six neuropeptides, vasoactive intestinal peptide, peptide histidine-methionine, substance P, methionine5-enkephalin, neuropeptide Y, and the bombesinlike intestinal peptides, in descending colon from 4 patients with idiopathic chronic constipation. Decreased concentrations of vasoactive intestinal peptide (707 +/- 112 ng/g wet tissue) and peptide histidine-methionine (543 +/- 58 ng/g) were found in the muscularis externa obtained from constipated patients compared with normal concentrations (40 patients) of vasoactive intestinal peptide (1199 +/- 47 ng/g) and peptide histidine-methionine (815 +/- 45 ng/g). Vasoactive intestinal peptide was identified by immunocytochemistry in nerve fibers within the circular smooth muscle layer of descending colon obtained from 6 control patients, but not in nerve fibers within the circular smooth muscle of descending colon obtained from 3 patients with idiopathic chronic constipation. By contrast, the distribution of immunoreactive met5-enkephalin was similar in normal descending colon and in descending colon obtained from patients with idiopathic chronic constipation. Decreased colonic concentrations of vasoactive intestinal peptide (a candidate nonadrenergic, noncholinergic inhibitory neurotransmitter) may be associated with diminution of inhibitory innervation of colonic circular smooth muscle in some patients with idiopathic chronic constipation.

Topics: Adult; Bombesin; Chronic Disease; Colon; Constipation; Enkephalin, Methionine; Female; Humans; Immunohistochemistry; Intestinal Mucosa; Male; Middle Aged; Muscle, Smooth; Peptide PHI; Radioimmunoassay; Substance P; Vasoactive Intestinal Peptide