AIM:To study the pharmacological profile and inhibition of smooth muscle contraction by YFa and its analogs in conjunction with their receptor selectivity. METHODS:The effects of YFa and its analogs (D-Ala2) YFa, Y (D...AIM:To study the pharmacological profile and inhibition of smooth muscle contraction by YFa and its analogs in conjunction with their receptor selectivity. METHODS:The effects of YFa and its analogs (D-Ala2) YFa, Y (D-Ala2) GFMKKKFMRF amide and Des-Phe-YGGFMKKKFMR amide in guinea pig ileum (GPI) and mouse vas deferens (MVD) motility were studied using an isolated tissue organ bath system, and morphine and DynA (1-13) served as controls. Acetylcholine was used for muscle stimulation. The observations were validated by specific antagonist pretreatment experiments using naloxonazine, naltrindole and norbinaltor-phimine norBNI. RESULTS:YFa did not demonstrate significant inhibition of GPI muscle contraction as compared with mor-phine (15% vs 62%, P = 0.0002), but moderate inhibition of MVD muscle contraction, indicating the role of κ opioid receptors in the contraction. A moderate inhibition of GPI muscles by (Des-Phe) YFa revealed the role of anti-opiate receptors in the smooth muscle contraction. (D-Ala-2) YFa showed significant inhibition of smooth muscle contraction, indicating the involvement of mainly δ receptors in MVD contraction. These results were supported by specific antagonist pretreatment assays. CONCLUSION:YFa revealed its side-effect-free analgesic properties with regard to arrest of gastroin-testinal transit. The study provides evidences for the involvement of κ and anti-opioid receptors in smooth muscle contraction.展开更多
Functional dyspepsia(FD)is a regularly diagnosed clinical gastrointestinal ailment with a high incidence rate that can considerably impact patients’health and quality of life and impose a substantial financial burden...Functional dyspepsia(FD)is a regularly diagnosed clinical gastrointestinal ailment with a high incidence rate that can considerably impact patients’health and quality of life and impose a substantial financial burden.Modern research on the pathophysiology of functional dyspepsia has not thoroughly explained the underlying reasons.The condition does not manifest any significant organ abnormalities,which raises the disease’s difficulty coefficient.Major pathogenic exceptions in FD include gastrointestinal motor dysfunction,gastrointestinal hormone secretion problem,visceral hypersensitivity,and brain-gut axis.Several ion channels have reportedly been implicated in the pathophysiological process of FD.Therefore,it is crucial to comprehend the probable activities of various ion channels in FD.This study focuses on the current state of research on the possible role of several ion channels in the pathogenesis of FD.展开更多
AIM: To investigate whether the reduction of stem cell factor (SCF) is mediated by decreased endogenous insulin-like growth factor (IGF)-1 in diabetic rat colon smooth muscle. METHODS: Sixteen Sprague-Dawley rats were...AIM: To investigate whether the reduction of stem cell factor (SCF) is mediated by decreased endogenous insulin-like growth factor (IGF)-1 in diabetic rat colon smooth muscle. METHODS: Sixteen Sprague-Dawley rats were randomly divided into two groups: control group and streptozotocin-induced diabetic group. After 8 wk of streptozotocin administration, colonic motility function and contractility of circular muscle strips were measured. The expression of endogenous IGF-1 and SCF was tested in colonic tissues. Colonic smooth muscle cells were cultured from normal adult rats. IGF-1 siRNA transfection was used to investigate whether SCF expression was affected by endogenous IGF-1 expression in smooth muscle cells, and IGF-1 induced SCF expression effects were studied. The effect of high glucose on the expression of endogenous IGF-1 and SCF was also investigated. RESULTS: Diabetic rats showed prolonged colonic transit time (252 ± 16 min vs 168 ± 9 min, P < 0.01) and weakness of circular muscle contraction (0.81 ± 0.09 g vs 2.48 ± 0.23 g, P < 0.01) compared with the control group. Endogenous IGF-1 and SCF protein expression was significantly reduced in the diabetic colonic muscle tissues. IGF-1 and SCF mRNA expression also showed a paralleled reduction in diabetic rats. In the IGF-1 siRNA transfected smooth muscle cells, SCF mRNA and protein expression was significantly decreased. IGF-1 could induce SCF expression in a concentration and time-dependent manner, mainly through the extracellular-signal-regulated kinase 1/2 signal pathway. High glucose inhibited endogenous IGF-1 and SCF expression and the addition of IGF-1 to the medium reversed the SCF expression. CONCLUSION: Myopathy may resolve in colonic motility dysfunction in diabetic rats. Deficiency of endogenous IGF-1 in colonic smooth muscle cells leads to reduction of SCF expression.展开更多
Over the last few years, the importance of the resident intestinal microbiota in the pathogenesis of several gastrointestinal diseases has been largely investigated. Growing evidence suggest that microbiota can influe...Over the last few years, the importance of the resident intestinal microbiota in the pathogenesis of several gastrointestinal diseases has been largely investigated. Growing evidence suggest that microbiota can influence gastrointestinal motility. The current working hypothesis is that dysbiosis-driven mucosal alterations induce the production of several inflammatory/immune mediators which affect gut neuro-muscular functions. Besides these indirect mucosal-mediated effects, the present review highlights that recent evidence suggests that microbiota can directly affect enteric nerves and smooth muscle cells functions through its metabolic products or bacterial molecular components translocated from the intestinal lumen. Tolllike receptors, the bacterial recognition receptors, are expressed both on enteric nerves and smooth muscle and are emerging as potential mediators between microbiota and the enteric neuromuscular apparatus. Furthermore, the ongoing studies on probiotics support the hypothesis that the neuromuscular apparatus may represent a target of intervention, thus opening new physiopathological and therapeutic scenarios.展开更多
AIM:To examine the effects of Padma Digestin on the smooth muscle motility of different gastrointestinal segments in vitro . METHODS:The effects of the ethanolic extract of Padma Digestin (at 8.16 mg/mL or 81.6mg/mL) ...AIM:To examine the effects of Padma Digestin on the smooth muscle motility of different gastrointestinal segments in vitro . METHODS:The effects of the ethanolic extract of Padma Digestin (at 8.16 mg/mL or 81.6mg/mL) on the contractility and susceptibility to acetylcholine (ACh) of muscle strips from the cardia, antrum, pylorus, duodenum, jejunum, ileum and colon of male Wistar rats were analyzed.RESULTS:Compared with the control treatment, the Padma Digestin extract had a procontractile effect on the antral smooth muscle strips. Padma Digestin decreased ACh sensitivity in cardia muscle strips and increased it in those from the antrum and pylorus. In the intestinal segments, spontaneous contractility was inhibited in both the duodenal and jejunal strips, whereas reactivity to ACh was inhibited in the jejunal strips only. In the colonic samples, Padma Digestin inhibited spontaneous and ACh-stimulated contractility at a low dose but seems to have increasing effects at a high dose. CONCLUSION:Padma Digestin extract has regionspecific effects on the contractility and excitability of gastrointestinal smooth muscle. Our results support the traditional use of Padma Digestin for maldigestion and functional gastrointestinal disorders.展开更多
A review is presented on the theories concerning the cause of pyloric stenosis with emphasis on the primary position of inherited hyperacidity in pathogenesis. Existing theories are critically analysed and the hyperac...A review is presented on the theories concerning the cause of pyloric stenosis with emphasis on the primary position of inherited hyperacidity in pathogenesis. Existing theories are critically analysed and the hyperacidity theory is precisely defined in the light of recent physiological insights into the gastrointestinal hormone motilin. The progressive fixed fasting hypergastrinaemia within the first few weeks of life will, in the baby who inherits acid secretion at the top of the normal range, produce hyperacidity of sufficient severity to trigger the process of acid-induced work hypertrophy of the pylorus. The potential contribution of motilin is discussed. The baby who inherits a normal gastric acidity will not reach acid levels severe enough to trigger sphincter hypertrophy despite the early gastrin stimulus. The potential threat will cease when gastrin naturally declines with age and the pyloric canal becomes wider. Genetic factors clearly must also be involved and these are separately discussed.展开更多
目的利用C57BL/6和W/W^v突变小鼠研究Cajal间质细胞(interstitial cells of Cajal,ICC)对小鼠胃肠各部位平滑肌条运动的影响,并通过胆碱能受体拮抗剂阿托品和钠通道阻断剂河豚毒素(tetrodotoxin,TTX)给药干预初步探讨氢溴酸槟榔碱(areco...目的利用C57BL/6和W/W^v突变小鼠研究Cajal间质细胞(interstitial cells of Cajal,ICC)对小鼠胃肠各部位平滑肌条运动的影响,并通过胆碱能受体拮抗剂阿托品和钠通道阻断剂河豚毒素(tetrodotoxin,TTX)给药干预初步探讨氢溴酸槟榔碱(arecoline hydrobromide,Ah)促进小鼠平滑肌条动力作用的机制。方法制备C57BL/6和W/W^v突变小鼠胃肠各部位(胃体、胃窦、空肠和结肠)平滑肌环形肌条标本,分别观察和记录2种小鼠离体胃肠各部位平滑肌条的运动,比较2种小鼠胃肠各部位肌条收缩情况(收缩振幅、收缩频率和张力),并观察Ah对2种小鼠胃肠各部位肌条收缩的影响及阿托品、TTX对Ah促动力作用的干预。结果C57BL/6小鼠胃体部平滑肌环形肌条的收缩为具有较高振幅储存食物和低频率少量推进性的收缩波形,胃窦部为高振幅高张力较高频率推进性的收缩波形,空肠部为低振幅高频率快速推进性的收缩波形,结肠部为分散性中等振幅和频率的收缩波形;W/W^v突变小鼠胃体部环形肌条的收缩频率、收缩振幅都在较低水平,张力较其他部位偏高,胃窦部收缩频率、收缩振幅和张力都在较高水平,空肠部的收缩频率仍是最高,收缩振幅和张力却最低,结肠部的收缩频率最低,收缩振幅和张力处于中等水平;C57BL/6小鼠各部位肌条的收缩力均远大于W/W^v突变小鼠(P<0.05,P<0.01,P<0.001);Ah能明显增加C57BL/6小鼠各部位肌条的收缩力(P<0.05,P<0.01,P<0.001),对W/W^v突变小鼠各部位肌条的收缩力只有轻微增加(P<0.05,P<0.001);阿托品能抑制Ah的促动力作用,而TTX并不能阻断。结论ICCs在调控小鼠胃肠平滑肌条运动中具有重要作用,氢溴酸槟榔碱的促动力作用机制除了ICCs网络的调控外,还有一部分神经调控。另外,氢溴酸槟榔碱可能是经M型受体起作用的。展开更多
基金Supported by Grants from the Administration of Lanzhou Scientific Technology,No.2010-1-88Gansu Natural Science Fund in China,No.1010RJZA111Natural Science Foundation of China,No.21272103 and No.81360540
文摘AIM: To investigate the effects and underlying mechanisms of resveratrol and genistein on contractile responses of rat gastrointestinal smooth muscle.
基金Supported by Council of Scientific and Industrial Research,Delhi
文摘AIM:To study the pharmacological profile and inhibition of smooth muscle contraction by YFa and its analogs in conjunction with their receptor selectivity. METHODS:The effects of YFa and its analogs (D-Ala2) YFa, Y (D-Ala2) GFMKKKFMRF amide and Des-Phe-YGGFMKKKFMR amide in guinea pig ileum (GPI) and mouse vas deferens (MVD) motility were studied using an isolated tissue organ bath system, and morphine and DynA (1-13) served as controls. Acetylcholine was used for muscle stimulation. The observations were validated by specific antagonist pretreatment experiments using naloxonazine, naltrindole and norbinaltor-phimine norBNI. RESULTS:YFa did not demonstrate significant inhibition of GPI muscle contraction as compared with mor-phine (15% vs 62%, P = 0.0002), but moderate inhibition of MVD muscle contraction, indicating the role of κ opioid receptors in the contraction. A moderate inhibition of GPI muscles by (Des-Phe) YFa revealed the role of anti-opiate receptors in the smooth muscle contraction. (D-Ala-2) YFa showed significant inhibition of smooth muscle contraction, indicating the involvement of mainly δ receptors in MVD contraction. These results were supported by specific antagonist pretreatment assays. CONCLUSION:YFa revealed its side-effect-free analgesic properties with regard to arrest of gastroin-testinal transit. The study provides evidences for the involvement of κ and anti-opioid receptors in smooth muscle contraction.
基金“Double first-class”construction project of Mongolian medicine scientific research and innovation team fund(190301)International cooperative scientific and technological innovation project of Mongolian medicine standardization research(MDK2018009)+1 种基金2018 National Civil Affairs Commission-Ministry of Education Mongolian Medicine R&D Engineering Key Laboratory Open Project(MDK2018056)Mongolian Medicine R&D National and Local Joint Engineering Research Center Open Fund Project(MDK2019044).
文摘Functional dyspepsia(FD)is a regularly diagnosed clinical gastrointestinal ailment with a high incidence rate that can considerably impact patients’health and quality of life and impose a substantial financial burden.Modern research on the pathophysiology of functional dyspepsia has not thoroughly explained the underlying reasons.The condition does not manifest any significant organ abnormalities,which raises the disease’s difficulty coefficient.Major pathogenic exceptions in FD include gastrointestinal motor dysfunction,gastrointestinal hormone secretion problem,visceral hypersensitivity,and brain-gut axis.Several ion channels have reportedly been implicated in the pathophysiological process of FD.Therefore,it is crucial to comprehend the probable activities of various ion channels in FD.This study focuses on the current state of research on the possible role of several ion channels in the pathogenesis of FD.
基金Supported by The National Natural Science Foundation of China, No. 30971354The International Cooperation Project of Jiangsu Province Department of Health, No. SBZ201100103The Graduate Innovation Foundation of Jiangsu Province, China,No. CXZZ11_0704
文摘AIM: To investigate whether the reduction of stem cell factor (SCF) is mediated by decreased endogenous insulin-like growth factor (IGF)-1 in diabetic rat colon smooth muscle. METHODS: Sixteen Sprague-Dawley rats were randomly divided into two groups: control group and streptozotocin-induced diabetic group. After 8 wk of streptozotocin administration, colonic motility function and contractility of circular muscle strips were measured. The expression of endogenous IGF-1 and SCF was tested in colonic tissues. Colonic smooth muscle cells were cultured from normal adult rats. IGF-1 siRNA transfection was used to investigate whether SCF expression was affected by endogenous IGF-1 expression in smooth muscle cells, and IGF-1 induced SCF expression effects were studied. The effect of high glucose on the expression of endogenous IGF-1 and SCF was also investigated. RESULTS: Diabetic rats showed prolonged colonic transit time (252 ± 16 min vs 168 ± 9 min, P < 0.01) and weakness of circular muscle contraction (0.81 ± 0.09 g vs 2.48 ± 0.23 g, P < 0.01) compared with the control group. Endogenous IGF-1 and SCF protein expression was significantly reduced in the diabetic colonic muscle tissues. IGF-1 and SCF mRNA expression also showed a paralleled reduction in diabetic rats. In the IGF-1 siRNA transfected smooth muscle cells, SCF mRNA and protein expression was significantly decreased. IGF-1 could induce SCF expression in a concentration and time-dependent manner, mainly through the extracellular-signal-regulated kinase 1/2 signal pathway. High glucose inhibited endogenous IGF-1 and SCF expression and the addition of IGF-1 to the medium reversed the SCF expression. CONCLUSION: Myopathy may resolve in colonic motility dysfunction in diabetic rats. Deficiency of endogenous IGF-1 in colonic smooth muscle cells leads to reduction of SCF expression.
文摘Over the last few years, the importance of the resident intestinal microbiota in the pathogenesis of several gastrointestinal diseases has been largely investigated. Growing evidence suggest that microbiota can influence gastrointestinal motility. The current working hypothesis is that dysbiosis-driven mucosal alterations induce the production of several inflammatory/immune mediators which affect gut neuro-muscular functions. Besides these indirect mucosal-mediated effects, the present review highlights that recent evidence suggests that microbiota can directly affect enteric nerves and smooth muscle cells functions through its metabolic products or bacterial molecular components translocated from the intestinal lumen. Tolllike receptors, the bacterial recognition receptors, are expressed both on enteric nerves and smooth muscle and are emerging as potential mediators between microbiota and the enteric neuromuscular apparatus. Furthermore, the ongoing studies on probiotics support the hypothesis that the neuromuscular apparatus may represent a target of intervention, thus opening new physiopathological and therapeutic scenarios.
文摘AIM:To examine the effects of Padma Digestin on the smooth muscle motility of different gastrointestinal segments in vitro . METHODS:The effects of the ethanolic extract of Padma Digestin (at 8.16 mg/mL or 81.6mg/mL) on the contractility and susceptibility to acetylcholine (ACh) of muscle strips from the cardia, antrum, pylorus, duodenum, jejunum, ileum and colon of male Wistar rats were analyzed.RESULTS:Compared with the control treatment, the Padma Digestin extract had a procontractile effect on the antral smooth muscle strips. Padma Digestin decreased ACh sensitivity in cardia muscle strips and increased it in those from the antrum and pylorus. In the intestinal segments, spontaneous contractility was inhibited in both the duodenal and jejunal strips, whereas reactivity to ACh was inhibited in the jejunal strips only. In the colonic samples, Padma Digestin inhibited spontaneous and ACh-stimulated contractility at a low dose but seems to have increasing effects at a high dose. CONCLUSION:Padma Digestin extract has regionspecific effects on the contractility and excitability of gastrointestinal smooth muscle. Our results support the traditional use of Padma Digestin for maldigestion and functional gastrointestinal disorders.
文摘A review is presented on the theories concerning the cause of pyloric stenosis with emphasis on the primary position of inherited hyperacidity in pathogenesis. Existing theories are critically analysed and the hyperacidity theory is precisely defined in the light of recent physiological insights into the gastrointestinal hormone motilin. The progressive fixed fasting hypergastrinaemia within the first few weeks of life will, in the baby who inherits acid secretion at the top of the normal range, produce hyperacidity of sufficient severity to trigger the process of acid-induced work hypertrophy of the pylorus. The potential contribution of motilin is discussed. The baby who inherits a normal gastric acidity will not reach acid levels severe enough to trigger sphincter hypertrophy despite the early gastrin stimulus. The potential threat will cease when gastrin naturally declines with age and the pyloric canal becomes wider. Genetic factors clearly must also be involved and these are separately discussed.
文摘目的利用C57BL/6和W/W^v突变小鼠研究Cajal间质细胞(interstitial cells of Cajal,ICC)对小鼠胃肠各部位平滑肌条运动的影响,并通过胆碱能受体拮抗剂阿托品和钠通道阻断剂河豚毒素(tetrodotoxin,TTX)给药干预初步探讨氢溴酸槟榔碱(arecoline hydrobromide,Ah)促进小鼠平滑肌条动力作用的机制。方法制备C57BL/6和W/W^v突变小鼠胃肠各部位(胃体、胃窦、空肠和结肠)平滑肌环形肌条标本,分别观察和记录2种小鼠离体胃肠各部位平滑肌条的运动,比较2种小鼠胃肠各部位肌条收缩情况(收缩振幅、收缩频率和张力),并观察Ah对2种小鼠胃肠各部位肌条收缩的影响及阿托品、TTX对Ah促动力作用的干预。结果C57BL/6小鼠胃体部平滑肌环形肌条的收缩为具有较高振幅储存食物和低频率少量推进性的收缩波形,胃窦部为高振幅高张力较高频率推进性的收缩波形,空肠部为低振幅高频率快速推进性的收缩波形,结肠部为分散性中等振幅和频率的收缩波形;W/W^v突变小鼠胃体部环形肌条的收缩频率、收缩振幅都在较低水平,张力较其他部位偏高,胃窦部收缩频率、收缩振幅和张力都在较高水平,空肠部的收缩频率仍是最高,收缩振幅和张力却最低,结肠部的收缩频率最低,收缩振幅和张力处于中等水平;C57BL/6小鼠各部位肌条的收缩力均远大于W/W^v突变小鼠(P<0.05,P<0.01,P<0.001);Ah能明显增加C57BL/6小鼠各部位肌条的收缩力(P<0.05,P<0.01,P<0.001),对W/W^v突变小鼠各部位肌条的收缩力只有轻微增加(P<0.05,P<0.001);阿托品能抑制Ah的促动力作用,而TTX并不能阻断。结论ICCs在调控小鼠胃肠平滑肌条运动中具有重要作用,氢溴酸槟榔碱的促动力作用机制除了ICCs网络的调控外,还有一部分神经调控。另外,氢溴酸槟榔碱可能是经M型受体起作用的。
