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Background: Abnormal expression of leptin and brain⁃derived neurotrophic factor (BDNF) is an important link in the occurrence of ulcerative colitis (UC), but the mechanism of leptin and BDNF in UC is still unclear. Aims: To explore the effect and mechanism of leptin and BDNF in DSS induced colitis in mice. Methods: Thirty⁃six male 8⁃10 weeks healthy leptin⁃deficient ob mice and leptin⁃normal expressing wild type (WT) mice were selected and randomly divided into WT experimental group, ob experimental group, WT control group and ob control group. The mice in experimental groups were given 3% DSS solution for 7 days to induce colitis model, and the mice in control group were given distilled water. After modeling, disease activity index (DAI) score, colon length, behavior and visceral sensitivity were observed. The mRNA expressions of leptin and BDNF in colon and hippocampus were detected by real⁃time fluorescent quantitative PCR, and the protein expression of BDNF in colon was detected by Western blotting. Results: Compared with corresponding control groups, DAI score, visceral sensitivity in WT experimental group and ob experimental group were significantly increased (P< 0.05), mRNA and protein expressions of BDNF in colon were significantly increased (P<0.05). Compared with WT control group, anxiety and depression⁃like behavior were found in WT experimental group, mRNA expressions of leptin, BDNF in hippocampus were significantly decreased (P<0.05). Correlation analysis showed that anxiety was positively correlated with length of colon in WT experimental group (P<0.05), and negatively correlated with DAI score (P<0.05); depression, expression of BDNF mRNA in colon were negatively correlated with length of colon (P<0.05), and positively correlated with DAI score (P<0.05); leptin in hippocampus was positively correlated with anxiety (P<0.05), while was negatively correlated with depression (P<0.05); expression of BDNF mRNA in colon was negatively correlated visceral sensitivity (P<0.05). Conclusions: Colonic BDNF secretion is associated with leptin expression, and both may be involved in the DSS⁃induced colitis in mice by mediating anxiety, depression and visceral sensitivity.
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Objective@#To investigate the effect of intestinal flora in children with functional constipation (FC) on expression of acid-sensitive Ion channel 3(ASIC3) in rats and their regulation in intestinal motility.@*Methods@#Faeces of FC children identified according to RomeⅣ criteria and healthy children from the First Affiliated Hospital of Anhui Medical University from December 2017 to June 2018 were collected, and then made into fecal microbiota solution.A pseudo - sterile rat model was established, according to the random number table method, and the rats were randomly divided into the treatment group and the control group, with 12 rats in each group, then the treatment group was given fecal microbiota solution of the children with FC and the control group was given fecal microbiota solution of the healthy children.The visceral sensitivity and intestinal propulsion rate of rats were determined by means of abdominal withdrawal reflex (AWR), while the intestinal microorganism of rats and children with FC were determined by 16SrDNA high-throughput sequencing, and the expressions of ASIC3 of intestinal in mRNA and protein were determined by adopting fluorescence quantitative PCR and Western blot.@*Results@#The species and quantity of intestinal flora of the children with FC and rats implanted with FC faecal bacteria were reduced(all P<0.05), and firmicutes and bacteroidetes were the main bacteria; compared to the control group, the small intestine propulsion rate(52% vs.74%) and visceral sensitivity(78 mmHg vs.63 mmHg) of the treated group were significantly decreased compared with those in the control group (all P<0.05); the mRNA (0.003 1±0.000 8 vs.0.012 4±0.002 5) and protein levels of ASIC3 (0.013 2±0.001 9 vs.0.072 1±0.008 7) in the small intestine were down-regulated significantly(all P<0.05); and the mRNA (0.002 8±0.000 7 vs.0.009 4±0.001 1) and protein levels of ASIC3(0.038 2±0.004 5 vs.0.089 7±0.009 4) in the colon were down-regulated significantly(all P<0.05).@*Conclusions@#Children with FC have intestinal flora disorder, and intestinal flora of FC children may affect intestinal motility by down-regulating the expression of intestinal ASIC3 in rats.
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Objective To explore the mechanism of vitamin D in the genesis of irritable bowel syndrome (IBS).Methods A total of 50 newborn Sprague Dawley (SD) rats were divided into three model groups and two control groups (saline control group and normal control group).The model was induced by dilute acetic acid enema.After rats were weaned,the rats of three IBS model groups were fed with normal diet,vitamin D deficient diet and vitamin D sufficient diet,respectively.The visceral sensitivity of the rats was assessed by the colorectal distention experiment.The intestinal tissues of rats was taken for histological score,and the intestinal mast cell (MC) was also counted.The mRNA level of vitamin D receptor (VDR) in colon tissues of rats was determined by real-time reverse transcription-polymerase chain reaction (RT-PCR).T test or rank sum test was performed for statistical analysis.Results When the water volume of balloon was 0.5 mL and 1.0 mL,the abdominal withdrawal reflex (AWR) scores of male rats of the vitamin D deficient model group were 2.67±0.33 and 3.60±0.28,which were higher than those of normal vitamin D model group (1.93±0.15 and 3.20±0.18),and the differences were statistically significant (t=4.491 and 2.683,both P＜0.05).When the water volume of balloon was 1.0 mL and 1.5 mL,the AWR scores of female rats of the vitamin D sufficient model group were 3.00 (3.00,3.00) and 3.33 (3.33,3.67),which were lower than those of normal vitamin D model group (3.67,3.33 to 4.00;and 4.00,4.00 to 4.00),and the differences were statistically significant (Z=-2.362 and-2.390,both P＜0.05).There was no statistically significant difference in histological scores of intestinal mucosal tissues of ileum distal segment and sigmoid between the model groups with different vitamin D concentration and saline control group as well as normal control group (all P＞0.05).The number of MC in the mucosal tissue of the sigmoid colon of female rats in IBS model group was 41.00± 19.80,which was higher than that in normal control group (12.40 ± 5.35),and the difference was statistically significant (t=3.118,P=0.030).The number of MC in the mucosal tissue of ileum of the female rats in vitamin D deficiency model group was 16.00 ± 3.71,which was higher than that in normal vitamin D model group (7.30± 2.66),and the difference was statistically significant (t =4.263,P =0.003).The VDR mRNA level in the colon tissues of male model rats of normal vitamin D model group was 1.48±0.33,which was higher than that of saline control group and normal control group (0.97± 0.21 and 1.00±0.21;t=2.590 and 2.482,both P＜0.05).The VDR mRNA levels in colon tissues of female rats of vitamin D deficient model group was 1.90 ± 0.66,which was higher than that of normal control group (1.00 ± 0.14),and the difference was statistically significant (t =2.649,P =0.038).Conclusions Vitamin D may affect visceral hypersensitivity in IBS,and MC may involve in vitamin D induced visceral hypersensitivity.
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ABSTRACT:Objective To investigate the role of PAR2 in the visceral sensitivity of IBS patients by observing the expression of rectal PAR2 in patients with irritable bowel syndrome and the effect of exogenous PAR2 on visceral sensitivity.Methods Based on Rome III criteria,16 patients with constipation predominant IBS (IBS-C),18 patients with diarrhea predominant IBS (IBS-D ),and 1 8 controls were selected from our hospital inpatient and outpatient departments. All the patients received colonoscopic examination and rectal mucosa biopsies. The expression of rectal mucosa PAR2 was observed by immunohistochemistry and Real-time fluorescence quantitative PCR.We studied the abdominal reactions by administering the PAR2 agonist in the rectal mucosa of rats to explore whether PAR2 is involved in visceral sensitivity.Results The results of PAR2 immunohistochemistry showed that PAR2 was mainly expressed in intestinal epithelial cells,especially in the villi;in addition,endothelial cells were also found positive.While the integral optical density (IA)of PAR2 expression did not significantly differ between IBS-D or IBS-C patients and controls according to the IPP image analysis.The PAR2 mRNA level in IBS-D or IBS-C patients was not significantly different from that of the control group by Real-time PCR analysis.There was no significant difference between the IBS-D and IBS-C groups.The EMG activity significantly increased in a volume-dependent manner during the rectal balloon expansion in the PAR2 agonist group.However,there was little EMG activity when the balloon was not dilated.The area under the curve in the PAR2 agonist group with 0 mL,0.4 mL and 0.6 mL of distension volume did not differ compared with that of the vehicle group.When the balloon volume increased to 0.8 mL,1.0 mL and 1.2 mL,the EMG activity was statistically significant (P<0.01)in the PAR2 agonist group compared with the control group.Conclusion PAR2 is highly expressed in the rectal mucosa of IBS patients.Administration of exogenous PAR2 agonist increases visceral sensitivity,suggesting that PAR2 is involved in visceral sensitivity.
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Objective To investigate the role of microRNA-490-5p (miR-490-5p) in the regulation of visceral sensitivity in rats with intestinal dysfunction.Methods The lentivirus vector system was used to construct the rno-miRNA-490-5p lentivirus expression vector.The rats were divided into normal group,diarrhea-predominant irritable bowel syndrome (IBS-D) group,lentivirus empty vector group and the siRNA silent group and the latter three groups were model groups.The efficiency of siRNA was measured by real-time polymerase chain reaction (PCR).The rats were gavaged with 10％ India ink,and then the time of first black stool,water content of feces and threshold of expansion capacity caused abdominal elevation or back arching were calculated.The visceral sensitivity of rats after miRNA-490-5p silenced was evaluated with abdominal withdrawal reflex (AWR) score by stimulating with different intensities of colonic dilatation.The abdominal electrical activity of rats stimulated by colonic distension was measured by BL-420F biological and functional experimental system.The change of the tension of rats isolated colon intestinal stimulated with acetylcholine chloride was also detected by BL-420F biological and functional experimental system.T test was used to compare the differences between the model groups and the normal group.One way analysis of variance was performed for multi-group comparison after miRNA-490-5p interfered.For comparison between two groups among multiple groups,least significant difference (LSD) method was used when the variance was equal,and Games-Howell method was used when the variance was unequal.Results The gastrointestinal propulsion time and the threshold of expansion capacity caused abdominal elevation or back arching of model groups were both lower than those of the normal group ((8.54±4.07) hvs (12.33±2.23) h,(0.56±0.08) mL vs (0.84±0.09) mL),and the differences were statistically significant (t =2.62 and 6.37,both P ＜ 0.05).After distension with 0.8 mL and 1.2 mL sodium chloride solution,the AWR scores of model groups were significantly higher than those of the normal group (3.20±0.56 vs 1.20±0.45,3.73±0.46 vs 2.60±0.55),and the differences were statistically significant (t=7.20 and 4.58,both P＜0.01).There was no significant difference in AWR score between the model groups and the normal group when distended with 1.6 mL sodium chloride solution (3.93 ±0.26 vs 3.80 ± 0.45) (P＞0.05).After miRNA-490-5p silenced,gastrointestinal propulsion time of normal group,IBS-D group,lentivirus empty vector group and the siRNA silent group was (11.12±1.01) h,(6.23±3.17) h,(6.09 ± 2.26) h and (12.36±1.97) h,and the differences among four groups were statistically significant (F=10.55,P＜0.01).The abdominal electrical activity of normal group,IBS-D group,lentivirus empty vector group and the siRNA silent group distension stimulated with 0.8 mL and 1.2 mL sodium chloride solution was (64.91 ± 10.50),(101.79 ±11.73),(80.49±1.27),(66.92±3.24) μV,and (105.09±52.40),(131.71± 16.74),(111.00±6.41) and (95.49± 4.2) μV,and the differences among four groups were statistically significant (F=16.82 and 9.14,both P＜0.05).There was no significant difference in abdominal electrical activity amplitude between silenced group and normal group ((66.92±3.24) μV vs (64.91±10.49) μV and (95.49±4.22) μV vs (105.09±2.40) μV) (all P＞ 0.05).After distension with 1.6 mL sodium chloride solution,the abdominal electrical activity amplitudeof silenced group was lower than the other groups,and the differences were statistically significant (F=11.09,P＜0.01).After adding 1∶1 000 acetylcholine chloride added,the tension of colon of normal group,IBS-D group,lentivirus empty vector group and the siRNA silent group increased by 0.71 ± 0.21,0.81±0.06,0.88±0.21 and 0.43±0.07,however there was no significant difference among the four groups (F=2.57,P =0.100).Conclusions Visceral hypersensitivity existed in rats with intestinal dysfunction.miRNA-490-5p may be involved in the regulation of visceral sensitivity.
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Objective:To evaluate visceral sensitivity,gut barrier function and autonomic nerve function (ANF) in patients with diarrhea-predominant irritable bowel syndrome (IBS-D),and to explore their roles in IBS-D pathophysiology.Methods:A total of 46 IBS-D patients (IBS-D group) were selected from the Department of Gastroenterology of China-Japan Friendship Hospital from October 2015 to March 2016,and 20 healthy volunteer were served as a control group (HC group).Clinical and psychological symptoms were evaluated by questionnaire,and visceral sensitivity to rectal balloon distention,gut barrier function and autonomic nerve function (ANF) were examined.The difference in the abovementioned indexes were compared between the 2 groups,and the correlations in the parameters were analyzed in the IBS-D group.Results:The scores of IBS symptom severity scale (IBS-SSS),Hamilton anxiety scale (HAMA),Hamilton depression scale (HAMD) and visceral sensitivity index (VSI) were significantly higher in the IBS-D group than those in the HC group (P＜0.01).In the visceral sensitivity test,maximum tolerable threshold in the IBS-D group was significantly decreased compared to that in the HC group (P＜0.01);there was no significant difference in first sensation threshold and defecating sensation threshold between the two groups (P＞0.05).As gut barrier function markers,the serum diamine oxidase (DAO) and d-lactate were significantly increased in the IBS-D group (P＜0.05).In ANF test,the total score and parasympathetic score as well as the proportion of abnormal scores in the IBS-D group were significantly higher than those in the HC group (P＜0.05).In IBS-D group,the HAMA,VSI and serum DAO were positively correlated with IBS-SSS (r=0.528,0.575,0.507;P＜0.01),while the 3 visceral sensitivity thresholds were negatively correlated with IBS-SSS (r=-0.636,-0.476,-0.697;P＜0.01);in addition to the IBS-SSS,the HAMA,HAMD,VSI and serum DAO were also significant negatively correlated with the visceral sensitivity thresholds (all P＜0.05);no significant correlations were found between the ANF and the other parameters.Conclusion:IBS-D patients show psychological symptoms,visceral hypersensitivity,impaired gut barrier function and abnormal ANF characterized by parasympathetic dysfunction;the former 3 factors are all associated with disease severity,and thus may play vital roles in IBS-D pathophysiology.
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Background:Tryptophan(TRP)is an essential amino acid,and can produce 5-hydroxytryptamine(5-HT)via 5-HT signal pathway and kynurenine( KYN)metabolic pathway under the catalysis of enzyme,thereby participating in the pathogenesis of visceral hypersensitivity in diarrhea-predominant irritable bowel syndrome(IBS-D). Aims:To investigate the relationship between visceral sensitivity and TRP metabolic pathway in patients with IBS-D. Methods:Thirty patients with IBS-D and 30 healthy controls from June 2012 to January 2014 at Guangdong Provincial TCM Hospital were enrolled. Score of gastrointestinal symptom rating scale( GSRS)was evaluated. Visceral sensitivity was measured by anorectal manometry. RT-PCR and Western blotting were used to detect mRNA and protein expressions of colon mucosal IDo, respectively. Serum 5-HT,5-HIAA,TRP,IDo,KYN,KYNA concentrations and IDo activity,KAT activity were determined by high performance liquid chromatography assay. Results:Compared with control group,GSRS score was significantly increased(P < 0. 05),initial perception threshold,defecation threshold,pain threshold were significantly decreased(P < 0. 05),anorectal constriction pressure was significantly increased( P < 0. 05),serum 5-HT,5-HIAA concentrations were significantly increased(P < 0. 05),mRNA and protein expressions of IDo were significantly increased (P < 0. 05),serum KYN was significantly increased(P < 0. 05),KYNA was significantly decreased(P < 0. 01),IDo activity was significantly incseased(P < 0. 01),and KAT activity was significantly decreased in IBS-D group(P < 0. 01). Correlation analysis showed that initial perception threshold,defecation threshold,pain threshold and anorectal constriction pressure were correlated with 5-HT,5-HIAA,TRP,KYN,KYNA,IDo activity and KAT activity in patients with IBS-D (P < 0. 05). Conclusions:TRP metabolic pathway is correlated with visceral hypersensitivity in patients with IBS-D.
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La sensibilidad visceral es una respuesta fisiológica normal de las estructuras huecas del tracto alimentario y su alteración (híper o hiposensibilidad) se ha involucrado en la génesis de la mayoría de los trastornos funcionales y su corrección o modulación fundamentan la mayoría de los esfuerzos actuales farmacológicos que buscan la supresión o alivio de síntomas asociados a estas alteraciones. La dispepsia funcional es un trastorno mal entendido fisiopatológicamente, lleno aún de equívocos diagnósticos y sujeto permanente de cambios en su definición, clasificación y enfoque terapéutico.Dada la prevalencia de la entidad parece útil revisar la conceptualización actual de la dispepsia y el papel de la sensibilidad visceral, como el elemento disparador fisiológico de la motilidad, en su fisiopatología.
Visceral sensitivity is a normal physiological response of digestive tract hollow structures. Hypersensitivity and hypo sensitivity have been involved in the genesis of most functional disorders. Currently correction or modulation is usually based on pharmacological efforts which seek to eliminate or alleviate symptoms associated with these disorders. Functional dyspepsia is a poorly understood physiopathological disorder still associated with diagnostic misunderstandings and permanently changing definition, classification and therapeutic approaches. Given the prevalence of this entity it seems useful to review the current conceptualization of dyspepsia and the role of visceral sensitivity as the physiological timer of motility in its physiopathology.
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Humans , Dyspepsia , Feeding and Eating Disorders , Gastrointestinal MotilityABSTRACT
Objective To observe the variation of tryptase expression in the colonic mucosa of patients with diarrhea-predominant irritable bowel syndrome(IBS-D) and the effects of their colonic mucosa cultured supernatants on mice visceral sensitivity. Methods The IBS-D patients study: of twenty-four patients with IBS-D and 12 healthy volunteers, four mucosal biopsies of each individual were collected at ascending colon under colonoscopy. The quantity of mucosal mast cells were detected by toluidine blue stains, and the tryptase concentration of colonic mucosa cultured supernatants were determined by enzyme-linked immunosorbent assay (ELISA). Animal experiments: fifty-six male six to eight weeks old C57BL/6 mice were divided into 7 groups and then were administrated with healthy volunteer's ascending colonic mucosa-cultured supernatants 100 μl (group A), IBS-D patient' s ascending colonic mucosa-cultured supernatants 100 μl (group B), IBS-D ascending colonic mucosacultured supernatants 100 μl with Fut-175(50 μg/ml, group C), tryptase with different concentration:0.6 ng (group D), 2.2 ng (group E), tryptase 2.2 ng with Fut-175 (group F), and 0.9% sodium chloride as control (group G) respectively. After six hours, the abdominal myoelectric activities (AMAs) were recorded during colorectal balloon distension (CRD), and the expressions of substance P (SP), Calcitonin gene-related peptide (CGRP) in spinal dorsal horn of lumbosaeral region were detected by immunohistochemistry. Results The number of mast cells in the ascending colon of patients with IBS-D [6.33 ± 1.64) / HP] was higher than that in controls [(3.08 ± 0.77 ) / HP], the difference was statistical significant (P = 0.000). The tryptase concentration of ascending colonic mucosa cultured supernatants in IBS-D patients [(0. 072 ± 0. 023) ng/mg] was higher than that in controls [(0.026 ± 0.014) ng/mg], the difference was statistical significant ( P = 0. 000). In animal experiments, when the inside pressure of balloon was 30, 45, 60 mmHg, respectively, the AMAs value in group B [(27.50±5.23), (41.69±5.80), (54. 03±6.13) μV, respectively] and group E [(27. 05±1.66), (40. 66±3.39), (54. 38± 4.68) μV, respectively] were significantly higher than those in group A, group C, group D, group F and group G (P＜0. 05, respectively). The average integrated option densities (IOD) of SP and CGRP in spinal dorsal horn in groupB (121.72 ± 4.67,123.54±4.32)and E (124.69±5.06,126.32±5.09) were higher than in group A, group C, group D,group F and group G (P＜0.05, respectively). Conclusion The quantity of mast cell and the content of tryptase in the ascending colonic mucosa of IBS-D patients increased significantly. And their colonic mucosa cultured supernatants caused the mice visceral hypersensitivity, which indicated that tryptase may involved in the variation of visceral sensitivity in IBS-D patients.
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Objective To study the effect of electromyographie biofeedback on visceralgia hypersensitivity in patients with refractory irritable bowel syndrome (IBS) and the relationship between psychological factors and vis-ceral hypersensitivity. Methods Sixty patients with refractory IBS were enrolled in this study and received electro-myographic biofeedback treatment for 4 weeks. The threshold of visceralgia, and scores on the Hamilton anxiety rating scale (HAMA) and the Hamilton depression rating scale (HAMD) were evaluated before and after treatment. Re-suits Compared with the baseline values, the threshold of visceralgia increased significantly during treatment(P≤ 0101) and the total scores on both the HAMA and HAMD had declined significantly (P≤0.01) by the end of 4, weeks of treatment. The evolution of the index of the threshold of visceralgia was negatively correlated with the evolu-tion of both the HAMA and HAMD scores (r = -0.543, P≤0.01; r = -0.728,P≤0.01). Conclusion Elec-tromyographic biofeedback treatment can elevate the threshold of visceralgia hypersensitivity in patients with refractory IBS. Anxiety and depression might contribute to visceralgia hypersensitivity in IBS.
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Objective To investigate the role of norepinephrine in the down-regulated visceral sensitivity of rats deprived of rapid eye movement(REM)sleep.Methods Twenty-four male Sprague- Dawley rats were randomly divided into 3 groups:cage-yoked rats as control(YC),rats with REM sleep deprivation(SD)and rats with yohimbine administered intraperitoneally after REM sleep deprivation(YSD).Flower pot technique was employed to make sleep deprivation model.YSD group was given vohimbine intraperitoneally at the 48th hour after REM sleep deprivation.After both SD and YSD groups had completed these processes,rats of all the three groups were given colorectal distension(CRD)and electromyogram (EMG)was recorded at the same time.The number of discharges of EMG and the threshold of Dain perception of the rats were observed to evaluate the visceral sensitivity.The thalamus,rectum and distal colon were taken after CRD;MAO-mRNA and TH-mRNA in three tissues were detected with RT-PCR.Resuits On 48th hour,the number of discharges of EMG in 10 seconds responding to CRD in group SD was significantly less than that in group YC and the threshold of pain perception in group SD was higher than that in group YC(P＜0.05).The number of discharge of EMG in group YSD was significantly more than that in group SD(P＜0.05).The expression of MAO-mRNA in group SD was lower than that in group YC(P＜0.05)and the expression of TH-mRNA in group SD was higher than that in group YC(P＜ 0.05).Conclusions The visceral sensitivity in rats is down-regulated by REM sleep deprivation,which can increase synthesis of norepinephrine.Norepinephrine can modulate visceral sensitivity.
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ObjectiveTo compare the difference effects on the proximal stomach in rapid(intake rate 100 mL/min) and slow(intake rate 15 mL/min) LNLT.Methods Forty healthy subjects received both the rapid and slow LNLTs.The caloric density of the nutrient was 1 kcal/mL. The TVDRI and MVDRI were recorded,and the corresponding TVPS and MVPS were measured by B-ultrasound.Results(1) There were positive correlation was identified between TVDRI and TVPS,and between MVDRI and MVPS in both slow and rapid LNLTs.(2) TVDRI and MVPS in slow LNLT were significantly smaller than those in rapid LNLT,but MVDRI was significantly larger in slow LNLT than that in rapid LNLT.(3) TVDRI was much closer to TVPS in slow LNLT than those in rapid LNLT.But MVDRI was much closer to MVPS in rapid LNLT than those in slow LNLT.Conclusion Both slow and rapid LNLTs could be used to evaluate the accommodation to a meal and visceral sensitivity of the proximal stomach.The visceral sensitivity is related to the accommodation function.TVDRI of slow LNLT is more sensitive in estimating the visceral sensitivity of the proximal stomach;MVDRI of rapid LNLT is more accurate in estimating the accommodation of the proximal stomach.
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Objective To investigate the effects of tegaserod on visceral sensitivity and explore the regulating mechanism.Methods Forty-two male Spragre-Dawley rats,which were induced colonic inflammation by intraluminal administration of trinitrobenzenesulfonic acid(TNBS),were randomly divided into eight groups.In the three colorectal distention(CRD) treated groups(n=6),abdominal contractions were recorded after 3,7 and 14 days of intra-gastric administration of tegaserod 2mg/kg d.In the three CRD control groups(n=4),abdominal contractions were recorded after 3,7 and 14 days of intra-gastric injection of saline 2.0mL/d.In immunohistochemistry(IH) treated group(n=6) and IH control group(n=6),samples of colon were removed and processed for SP and CGRP immunohistochemistry after 7 days of intra-gastric administration of tegaserod and saline,respectively.Results Abdominal contractions induced by colonic distention decreased significantly at 1.2mL and 1.6mL distention volume after 3 days of tegaserod administration(P
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Objective To study the influence of partial restraint stress (PRS) on visceral sensitivity and plasma 5-hydroxytryptamine (5-HT) concentration in rats and to study the effects of 5-HT 4 receptor agonist and antagonist on visceral sensitivity and plasma 5-HT level in rats under PRS.Methods Male Wistar rats (n=32) were divided into four test groups. After two hours of PRS or sham-stress, 1-methyl-2-pyrrolidinone (solvent), tegaserod(a partial 5-HT 4 receptor agonist), and GR113808(a 5-HT 4 receptor antagonist) were administered intraperitoneally to the corresponding groups respectively. Thirty minutes after intraperitoneal injection, visceral sensitivity of rats, which was reflected by abdominal cramps induced by rectal distension, was recorded. Rectal distension was performed by insertion and inflation of a balloon(0.4-1.2 ml). Abdominal contractions were recorded by electromyography. Plasma 5-HT concentration was determined by fluorometry. Results Stress enhanced the number of abdominal cramps induced by rectal distension compared with sham-stress for all volumes of distension (0.4 ml:10.00?3.74 vs. 6.57?1.40; 0.8 ml: 16.75?2.92 vs.11.86?3.44; 1.2 ml: 19.50?4.24 vs. 14.86?3.19,P