Oxytocin decreases colonic motility of cold water stressed rats via oxytocin receptors

AIM: To investigate whether cold water intake into the stomach affects colonic motility and the involvement of the oxytocin-oxytocin receptor pathway in rats. METHODS: Female Sprague Dawley rats were used and some of them were ovariectomized. The rats were subjected to gastric instillation with cold (0-4 degrees C, cold group) or room temperature (20-25 degrees C, control group) saline for 14 consecutive days. Colon transit was determined with a bead inserted into the colon. Colonic longitudinal muscle strips were prepared to investigate the response to oxytocin in vitro. Plasma concentration of oxytocin was detected by ELISA. Oxytocin receptor expression was investigated by Western blot analysis. Immunohistochemistry was used to locate oxytocin receptors. RESULTS: Colon transit was slower in the cold group than in the control group (P < 0.05). Colonic smooth muscle contractile response to oxytocin decreased, and the inhibitory effect of oxytocin on muscle contractility was enhanced by cold water intake (0.69 +/- 0.08 vs 0.88 +/- 0.16, P < 0.05). Atosiban and tetrodotoxin inhibited the effect of oxytocin on colonic motility. Oxytocin receptors were located in the myenteric plexus, and their expression was up-regulated in the cold group (P < 0.05). Cold water intake increased blood concentration of oxytocin, but this effect was attenuated in ovariectomized rats (286.99 +/- 83.72 pg/mL vs 100.56 +/- 92.71 pg/mL, P < 0.05). However, in ovariectomized rats, estradiol treatment increased blood oxytocin, and the response of colonic muscle strips to oxytocin was attenuated. CONCLUSION: Cold water intake inhibits colonic motility partially through oxytocin-oxytocin receptor signaling in the myenteric nervous system pathway, which is estrogen dependent. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Involvement of nitrergic neurons in colonic motility in a rat model of ulcerative colitis

BACKGROUND The mechanisms underlying gastrointestinal(GI)dysmotility with ulcerative colitis(UC)have not been fully elucidated.The enteric nervous system(ENS)plays an essential role in the GI motility.As a vital neurotransmitter in the ENS,the gas neurotransmitter nitric oxide(NO)may impact the colonic motility.In this study,dextran sulfate sodium(DSS)-induced UC rat model was used for investigating the effects of NO by examining the effects of rate-limiting enzyme nitric oxide synthase(NOS)changes on the colonic motility as well as the role of the ENS in the colonic motility during UC.AIM To reveal the relationship between the effects of NOS expression changes in NOS-containing nitrergic neurons and the colonic motility in a rat UC model.METHODS Male rats(n=8/each group)were randomly divided into a control(CG),a UC group(EG1),a UC+thrombin derived polypeptide 508 trifluoroacetic acid(TP508TFA;an NOS agonist)group(EG2),and a UC+NG-monomethyl-L-arginine monoacetate(L-NMMA;an NOS inhibitor)group(EG3).UC was induced by administering 5.5%DSS in drinking water without any other treatment(EG1),while the EG2 and EG3 were gavaged with TP508 TFA and L-NMMA,respectively.The disease activity index(DAI)and histological assessment were recorded for each group,whereas the changes in the proportion of colonic nitrergic neurons were counted using immunofluorescence histochemical staining,Western blot,and enzyme linked immunosorbent assay,respectively.In addition,the contractile tension changes in the circular and longitudinal muscles of the rat colon were investigated in vitro using an organ bath system.RESULTS The proportion of NOS-positive neurons within the colonic myenteric plexus(MP),the relative expression of NOS,and the NOS concentration in serum and colonic tissues were significantly elevated in EG1,EG2,and EG3 compared with CG rats.In UC rats,stimulation with agonists and inhibitors led to variable degrees of increase or decrease for each indicator in the EG2 and EG3.When the rats in EGs developed UC,the mean contraction tension of the colonic smooth muscle detected in vitro was higher in the EG1,EG2,and EG3 than in the CG group.Compared with the EG1,the contraction amplitude and mean contraction tension of the circular and longitudinal muscles of the colon in the EG2 and EG3 were enhanced and attenuated,respectively.Thus,during UC,regulation of the expression of NOS within the MP improved the intestinal motility,thereby favoring the recovery of intestinal functions.CONCLUSION In UC rats,an increased number of nitrergic neurons in the colonic MP leads to the attenuation of colonic motor function.To intervene NOS activity might modulate the function of nitrergic neurons in the colonic MP and prevent colonic motor dysfunction.These results might provide clues for a novel approach to alleviate diarrhea symptoms of UC patients.

Extended Fasting Durations Delayed Gastric Emptying and Colonic Motility in Normal Male Rats

Background: Previous studies on fasting and gastrointestinal motility were reported with information lacking concerning prolonged continuous fasting and gastrointestinal motility. This study investigated the effect of prolonged fasting duration on gastrointestinal motility. Methods: Forty-five (45) male Wistar rats, with body weights between 180 - 200 g were used. They were randomly assigned into three (3) groups. Group1: control (rats fasted for 18 h—common duration of fasting for motility studies), groups 2 and 3 fasted for 48 and 72 h respectively. Five (5) rats per experiment and per group were considered. Blood glucose was determined by glucose oxidase method, gastric emptying was assessed by hydrated carbohydrate meal, intestinal motility by charcoal meal, and colonic motility was assessed using bead test. Data were reported in Mean ± SEM and analyzed with one-way ANOVA. Differences in results were considered significant at p ≤ 0.05. Results: There was no significant change in the blood glucose level (mmol/L) of rats in the 48 h group (2.94 ± 0.35) and 72 h group (3.20 ± 0.32) as compared with the control (3.62 ± 0.19). There was a significant decrease in the rate of gastric emptying (g) in the 72 h group (0.20 ± 0.08) compared with the control (0.64 ± 0.16). The intestinal transit (cm) in the 48 h group (67.54 ± 6.15) and 72 h group (72.10 ± 7.60) increased significantly when compared with the control (42.14 ± 3.14). There was a significant decrease in the colonic motility time (Sec.) in the 48 h group (2707 ± 864.1) and 72 h group (6363 ± 968.1) when compared with the control (263.8 ± 64.26). Conclusion: Extended fasting durations decrease the rate of gastric emptying and colonic motility. It suggests that extended fasting durations could be beneficial in intestinal spasms or where the gut is required to relax.

Normal aspects of colorectal motility and abnormalities in slow transit constipation

Human colonic motility is a relatively difficult topic to investigate. However, the refinement of manometric techniques in recent years enabled us to study both the proximal and distal segments of the viscus. The present paper reviews our knowledge about normal aspects of colorectal motility in man and the abnormalities found in slow transit constipation (STC), one of the most frequent and difficult to treat subtypes of constipation. An internetbased search strategy of the Medline and Science Citation Index was performed using the keywords colon, colonic, colorectal, constipation, slow transit, motility, rectal, rectum in various combinations with the Boolean operators AND, OR and NOT. Only articles related to human studies were used, and manual cross-referencing was also performed. Most of colonic motor activity is represented by single nonpropagated contractions, rarely organized in bursts; this activity is maximal during the day, especially after waking and following meals. In addition, a specialized propagated activity with propulsive features is detectable, represented by high-and low-amplitude propagated contractions. In the severe form of constipation represented by the slow transit type, the above motor activity is completely deranged. In fact, both basal segmental activity (especially in response to meals) and propagated activity (especially that of high amplitude) are usually decreased, and this may represent a physiologic marker of this disorder. Human colonic motor activity is quite a complex issue, still only partly understood and investigated, due to anatomic and physiological difficulties. In recent years, however, some more data have been obtained, even in proximal segments. These data have helped in elucidating, although only in part, some pathophysiological mechanisms of chronic constipation, and especially of the STC subtype.

THE COLONIC TRANSIT TEST IN THE ASSESSMENT OF CHRONIC CONSTIPATION

In order to assess colonic motility of chronic constipation, colonic transit test was carried out in 34 patients with chronic constipation and in 20 healthy subjects. 20 radiopaque markers are ingested at 8 am before the day test, and plain abdominal films were obtained at 24 h, 48 h and 72 h. The normal value of colonic transit test was 16(80%), or more markers passed after 72 h. By means of transit time study, 34 constipated patients were classified into 2 groups: 12 normal transit patients and 22 slow transit patients. There was no difference in colonic transit time between normal transit patients and controls (P>005). Patients with slow transit had more markers left in right colon, left colon and rectosigmoid colon at 48 h (P<001, respectively) and 72 h (P<001, respectively). According to the transit index, 22 slow transit patients were divided into 3 types: 10 cases colonic stasis, 8 cases outlet obstruction and 4 cases colorectal stasis. The study suggests that chronic constipated patients have abnormalbilities of colonic transit.

Role of nitric oxide in the impairment of circular muscle contractility of distended, uninflamed mid-colon in TNBS-induced acute distal colitis in rats

AIM： To evaluate the role of nitric oxide （NO） in the motor disorders of the dilated uninflamed mid-colon （DUMC） from trinitrobenzene sulfonic acid （TNBS）-induced acute distal colitis in rats. METHODS： Colitis was induced in male Sprague-Dawley rats by a single intracolonic administration of TNBS. Control rats received an enema of 0.9% saline. The rats were killed 48 h after TNBS or saline administration. Macroscopic and histologic lesions of the colon were evaluated. Myeloperoxidase （MPO） and nitric oxide synthase （NOS） activity were measured on the colonic tissue. In TNBS rats, we evaluated spontaneous and evoked contractile activity in circular muscle strips derived from DUMC in comparison to the same colonic segment of control rats, both in the presence and in the absence of a non-selective NOS isoforms inhibitor N-nitro-L- arginine （L-NNA）. Pharmacological characterization of electric field stimulation （EFS）-evoked contractile responses was also performed. RESULTS： In TNBS rats, the distal colon showed severe histological lesions and a high MPO activity, while the DUMC exhibited normal histology and MPO activity. Constitutive NOS activity was similar in TNBS and control rats, whereas inducible NOS activity was significantly increased only in the injured distal colon of TNBS rats. Isometrically recorded mechanical activity of circular muscle strips from DUMC of TNBS rats showed a marked reduction of the force and frequency of spontaneous contractions compared to controls, as well as of the contractile responses to a contracting stimulus. In the presence of L-NNA, the contractile activity and responses displayed a significantly greater enhancement compared to controls. The pharmacological characterization of EFS contractile responses showed that a cooperative-like interaction between cholinergic muscarinic and tachyldnergic neurokinin 1 and 2 receptors mediated transmission in DUMC of TNBS rats vs a simple additive interaction in controls. CONCLUSION： The results of this study show that, during TNBS-induced acute distal colitis, circular muscle intrinsic contractile mechanisms and possible enteric neural excitatory activity are inhibited in the distended uninflamed mid-colon. Suppression of NO synthesis markedly improves spontaneous and evokes muscle contractions, in spite of any evident change in local NO activity. 2005 The WJG Press and Elsevier Inc. All rights reserved

Consensus statement AIGO/SICCR:Diagnosis and treatment of chronic constipation and obstructed defecation(partⅠ:Diagnosis)

Chronic constipation is a common and extremely troublesome disorder that significantly reduces the quality of life,and this fact is consistent with the high rate at which health care is sought for this condition.The aim of this project was to develop a consensus for the diagnosis and treatment of chronic constipation and obstructed defecation.The commission presents its results in a "Question-Answer" format,including a set of graded recommendations based on a systematic review of the literature and evidence-based medicine.This section represents the consensus for the diagnosis.The history includes information relating to the onset and duration of symptoms and may reveal secondary causes of constipation.The presence of alarm symptoms and risk factors requires investigation.The physical examination should assess the presence of lesions in the anal and perianal region.The evidence does not support the routine use of blood testing and colonoscopy or barium enema for constipation.Various scoring systems are available to quantify the severity of constipation;the Constipation Severity Instrument for constipation and the obstructed defecation syndrome score for obstructed defecation are the most reliable.The Constipation-Related Quality of Life is an excellent tool for evaluating the patient's quality of life.No single test provides a pathophysiological basis for constipation.Colonic transit and anorectal manometry define the pathophysiologic subtypes.Balloon expulsion is a simple screening test for defecatory disorders,but it does not define the mechanisms.Defecography detects structural abnormalities and assesses functional parameters.Magnetic resonance imaging and/or pelvic floor sonography can further complement defecography by providing information on the movement of the pelvic floor and the organs that it supports.All these investigations are indicated to differentiate between slow transit constipation and obstructed defecation because the treatments differ between these conditions.

Distribution,function and physiological role of melatonin in the lower gut

Melatonin is a hormone with endocrine, paracrine andautocrine actions. It is involved in the regulation of multiple functions, including the control of the gastroin-testinal (GI) system under physiological and pathophys-iological conditions. Since the gut contains at least 400times more melatonin than the pineal gland, a reviewof the functional importance of melatonin in the gutseems useful, especially in the context of recent clinicaltrials. Melatonin exerts its physiological effects throughspecific membrane receptors, named melatonin-1 re-ceptor (MT1), MT2 and MT3. These receptors can befound in the gut and their involvement in the regulationof GI motility, inflammation and pain has been reportedin numerous basic and clinical studies. Stable levels ofmelatonin in the lower gut that are unchanged follow-ing a pinealectomy suggest local synthesis and, further more, implicate physiological importance of endogenous melatonin in the GI tract. Presently, only a small number of human studies report possible beneficial and also possible harmful effects of melatonin in case reports and clinical trials. These human studies include patients with lower GI diseases, especially patients with irritable bowel syndrome, inflammatory bowel disease and colorectal cancer. In this review, we summarize the presently available information on melatonin effects in the lower gut and discuss available in vitro and in vivo data. We furthermore aim to evaluate whether melatonin may be useful in future treatment of symptoms or diseases involving the lower gut.

Outcomes and prognostic factors of fecal microbiota transplantation in patients with slow transit constipation:results from a prospective study with long-term follow-up

Background and aim:Gutmicrobiotamay contribute to regulate colonicmotility,which is involved in the etiology of constipation.Fecalmicrobiota transplantation(FMT)has been demonstrated to restore intestinal homeostasis.The aimof this study was to evaluate the clinical outcomes and prognostic factors of FMT for the treatment of slow transit constipation(STC).Methods:Fifty-two patients with STC received standardized FMT and were followed up for 6 months.Bowel habit,colonic transit time,constipation-related symptoms(PAC-SYM score),quality of life(PAC-QOL score),treatment satisfaction scores and adverse events were monitored.The primary efficacy endpoint was the proportion of patients having on average three or more complete spontaneous bowel movements(CSBMs)per week.Results:The primary efficacy endpoint was achieved in 50.0%,38.5%and 32.7%of patients over week intervals 3–4,9–12 and 21–24,respectively(P<0.01 for all comparisons).Significant improvements were also observed in other bowel movement assessments,colonic transit time,constipation-related symptoms and quality of life;but all improvements diminished at weeks 12 and 24.Incompleteness of evacuation served as the only factor associated with efficacy.No serious treatmentrelated adverse events were observed.Conclusion:This study suggested FMT was effective and safe for STC,while a late loss of efficacy was also observed.A lower degree of sensation of incompleteness predicted a better outcome.