桂枝油对兔离体肠平滑肌的运动作用机制

目的:观察桂枝油对兔离体肠平滑肌的肌张力影响变化,探讨桂枝油治疗肠易激综合征的作用机制。方法:采用兔离体肠平滑肌肌条,用BL-410生物机能实验系统肌张力传感器测量肌条收缩与舒张的幅值。结果:桂枝油高剂量能抑制兔离体肠平滑肌自律性肌张力,收缩张力(g)由(4.9±0.8)降至(4.0±0.4),差异有显著性(P<0.01);抑制由乙酰胆碱,组胺和氯化钡所致的兔离体肠痉挛性收缩,高中低各剂量组经统计学分析,差异有显著性(P<0.01)。结论:桂枝油能降低细胞内钙的释放,可能是由于阻滞Ca2+通过L-型Ca2+通道进入细胞内,最终使细胞内钙降低,平滑肌舒张而达到解除肠易激综合征引起的胃肠疼痛。     

冬凌草甲素对家兔肠平滑肌活动的影响

目的 探讨冬凌草甲素对家兔离体肠道平滑肌的影响.方法 以家兔肠张力为指标,给予同一离体盲肠相同剂量的冬凌草甲素粗提物水溶液、乙酰胆碱、硫酸阿托品、新斯的明,对比不同影响;给予不同剂量的冬凌草甲素粗提物水溶液,对比不同影响.结果 冬凌草甲素对家兔肠平滑肌张力无明显影响.结论 家兔肠平滑肌对冬凌草甲素不敏感,这为冬凌草甲素的临床应用提供了可靠的生理依据.     

老龙七水提液对兔离体肠平滑肌收缩的影响

目的:研究老龙七水提液对兔离体肠平滑肌收缩的影响。方法:以0.25、0.50、0.75、1.00、1.25 g(生药)/L老龙七水提液、0.003 125 g/L乙酰胆碱(先加入)+1.25 g(生药)/L老龙七水提液(后加入)、0.003 125 g/L阿托品(先加入)+1.25 g(生药)/L老龙七水提液(后加入)作用于兔离体肠平滑肌,记录兔离体肠平滑肌收缩频率、振幅和张力。结果:0.75~1.25 g(生药)/L老龙七水提液可明显增强兔离体肠平滑肌自发性收缩的振幅和张力(P<0.01),且呈浓度依赖性,但对频率无影响;1.25 g(生药)/L老龙七水提液可明显增强乙酰胆碱诱导的兔离体肠平滑肌收缩的振幅和张力(P<0.05),并且可明显增强阿托品诱导的兔离体肠平滑肌舒张后的振幅和张力(P<0.05)。结论:老龙七水提液可增强乙酰胆碱诱导的兔离体肠平滑肌的收缩,可对抗阿托品诱导的兔离体肠平滑肌舒张。     

煨制川木香对家兔离体肠肌解痉作用的研究

目的:研究煨制川木香对家兔离体肠肌的解痉作用。方法:用Magnus离体肠肌累积剂量法观察煨制川木香石油醚部位对家兔离体肠管作用的量效关系,及其对乙酰胆碱、磷酸组胺及氯化钡(Bacl2)所致家兔肠管痉挛的影响。结果:煨制川木香石油醚部位对家兔离体肠管收缩的抑制作用呈一定的量效关系,表现出拮抗乙酰胆碱、磷酸组胺及Bacl2的作用。结论:煨制川木香石油醚部位对正常离体肠肌具有抑制作用,且随剂量增加而作用增强。其机制可能与乙酰胆碱、组胺竞争,阻断M、H1受体,并直接抑制肠肌兴奋性有关。     

RS67506对肠道运动的影响

目的研究5-羟色胺(5-HT)4受体激动剂RS67506对小鼠肠推进运动和对大鼠离体小肠肌条运动的影响。方法应用炭末法和张力换能器分别观察RS67506对小鼠肠推进运动和对大鼠离体小肠肌条的平均收缩幅度、收缩频率和静息张力的影响,并与Cisapride的作用相比较。结果 RS67506在小剂量时对小鼠肠推进运动无明显作用,中剂量和大剂量时作用明显,并且RS67506剂量依赖性增强肌条的收缩幅度,但对肌条收缩频率和静息张力无明显作用。结论 RS67506在剂量稍大的条件下,具有与Cisapride相当的对小鼠肠推进运动的作用。它对大鼠离体小肠肌条的收缩幅度与Cisapride相似,具有剂量依赖性增强作用,如果事先加入5-HT4受体拮抗剂RS23597-190,RS67506无明显作用,这表明RS67506对平滑肌肌条的作用是通过5-HT4受体完成的。     

肠复贴对肠运动功能影响的研究

目的研究肠复贴对肠运动功能的影响。方法通过墨汁推进实验观察其对正常小鼠小肠以及在阿托品和新斯的明作用下、大鼠大肠推进运动的体内体外研究,评价肠复贴对肠运动功能的影响。结果肠复贴对正常小鼠小肠推进运动显著增强,能明显促进大鼠大肠推进作用。结论肠复贴对胃肠平滑肌有兴奋作用,能促进肠内容物的推进,加快排出肠腔积气和积物。     

骆驼蓬对肠平滑肌的影响

本实验观察了骆驼蓬乙醇浸膏对动物在体、离体肠平滑肌自发性、药物性活动的影响。结果表明,骆驼蓬乙醇浸膏具有明显增强小鼠小肠推进性蠕动作用。对兔离体正常肠平滑肌依给药剂量不同表现小剂量收缩、大剂量舒张的双向调节作用。亦显示出具有能对抗酚妥拉明、氯化钡、毒扁豆碱、乙酰胆碱所引起的离体肠平滑肌收缩反应的作用。     

山楂水提物对大鼠离体胃、肠平滑肌条收缩性的影响研究

目的:研究山楂水提物对大鼠离体胃、肠平滑肌条收缩性的影响。方法:以大鼠离体胃、肠平滑肌条为研究对象,观察在正常克氏液条件下加入山楂水提物后大鼠胃、肠平滑肌条的收缩状况及在乙酰胆碱、阿托品作用下加入山楂水提物后大鼠肠平滑肌条的收缩状况。结果:山楂水提物在5～20mg·mL-1浓度范围内可显著增强大鼠胃、肠平滑肌条的运动,且具有显著剂量依赖性。山楂水提物(20mg·mL-1)可加强乙酰胆碱引起的肠平滑肌的强烈收缩,对抗阿托品引起的肠平滑肌的舒张作用。结论:山楂水提物对大鼠胃、肠平滑肌条的收缩具有显著的刺激作用。     

藿香正气滴丸对正常及乙酰胆碱刺激下动物胃肠道功能的影响

目的:观察藿香正气滴丸对正常及乙酰胆碱刺激下动物胃肠功能的影响。方法:观察藿香正气滴丸对正常小鼠胃排空和肠推进运动、乙酰胆碱所致大鼠离体胃底条平滑肌收缩、家兔离体肠平滑肌收缩作用以及家兔在体肠平滑肌收缩作用的影响。结果:藿香正气滴丸对正常状态胃肠运动无明显影响;可不同程度抑制乙酰胆碱引起的家兔在体回肠平滑肌收缩幅度以及乙酰胆碱所致大鼠离体胃底平滑肌以及家兔离体十二指肠平滑肌的收缩。结论:藿香正气滴丸对不同状态的胃肠道具有不同影响,对过度兴奋的胃肠道平滑肌收缩具有抑制作用,而对正常状态的胃肠道无明显影响。     

益智仁醇提取物对动物胃肠运动的影响

目的:研究益智仁醇提取物对动物胃肠运动的影响。方法:采用小鼠在体胃肠运动实验和家兔离体肠肌运动实验,观察益智仁醇提取物对正常小鼠胃排空、小肠推进运动和家兔离体肠肌收缩的影响。结果:益智仁醇提取物在5、10、20g·kg-1剂量下给药对正常小鼠胃排空有显著抑制作用,对家兔离体肠肌收缩有显著抑制作用,对氯化乙酰胆碱引起的肠肌兴奋有显著拮抗作用。结论:益智仁醇提取物对动物胃肠运动有抑制作用,其作用途径可能与M胆碱受体有关。     

Effects of hexoestrol on the contractility of the isolated,blood-perfused canine papillary muscle and of the guinea-pig ileum

Summary The effects of hexoestrol were studied on the blood flow and the tension development of the isolated, blood-perfused papillary muscle of the dog, as well as on the contractions of the guinea-pig ileum induced by acetylcholine, histamine or BaCl₂. Hexoestrol caused an increase in coronary blood flow and a negative inotropic effect in a dose-dependent manner. High doses of hexoestrol produced a loss of contractility of the papillary muscle without significant alterations of the amplitude and shape of the electrical activity recorded extracellularly. Hexoestrol had a strong non-selective relaxant effect on the guinea-pig ileum and was 10–20 times more potent than papaverine in antagonizing contractions induced by the 3 agonists. These results indicate that hexoestrol probably acts by blocking certain steps in the process by which extracellular and/or superficially bound Ca ions move to the contractile machinery in cardiac and in smooth muscle cells. Thus, it may bear some resemblance to the so-called calcium antagonists.     

干酪菌发酵产物对豚鼠离体回肠平滑肌收缩功能的影响

目的 观察干酪菌发酵产物对豚鼠离体回肠平滑肌收缩功能的影响。方法采用豚鼠离体回肠平滑肌标本,观察加入干酪菌发酵产物前后肌紧张的变化以及加入几种受体阻断剂对其药效的影响。结果 干酪菌发酵产物能提高豚鼠离体回肠平滑肌肌紧张,且呈剂量-效应依赖关系,组织胺H1受体阻断剂苯海拉明能阻断其兴奋作用。结论 干酪菌发酵产物能提高豚鼠离体回肠平滑肌肌紧张,其作用途径与组织胺H1受体有关。     

INTESTINAL MOTILITY DISORDER INDUCED BY FREE RADICALS: A NEW MODEL MIMICKING OXIDATIVE STRESS IN GUT

Literature data suggest that the inflamed intestine may be subjected to a considerable oxidative stress. Therefore, the aim of the present study was to simulate the oxidative stress in the gastrointestinal tract and to explore its effect on intestinal motility. This was attained by treating isolated segments from the rabbit jejunum and from the guinea pig ileum with 2,2'-Azobis (2-amidinopropane) dihydrochloride (ABAP), which generates peroxyl radicals by thermal decomposition. Treatment of intestinal segments with ABAP reduced the muscarinic cholinergic response to acetylcholine in both preparations and induced a dose-dependent inhibition of the spontaneous contractions in the jejunum, also in the presence of tetrodotoxin. ABAP was found to inhibit the contractile response induced by BaCl(2) in guinea pig ileum preparations. This effect was not dose-dependent and it was reversed by Bay-K 8644, which activates voltage operated L-type calcium channels. The rapid and reversible effects of ABAP suggest that it might directly affect L-type calcium channels before lipoperoxidation induction. In conclusion, the results of the present study show that ABAP could be a useful tool to simulate early contractility dysfunctions mediated by oxidative stress.     

Effects of neurotensin on isolated intestinal smooth muscles

The effects of neurotensin were investigated in intestinal smooth muscle preparations. Neurotensin relaxed the rat ileum, and contracted the guinea-pig ileum and taenia. Neurotensin induced a biphasic response (relaxation followed by contraction) in the contracted guinea-pig ileum. In all systems, half-maximal effects were obtained with 4–5 nM neurotensin and maximal responses with 30–60 nM; tachyphylaxis occurred with higher concentrations. Tetrodotoxin did not affect the responses to neurotensin in the rat ileum and the guinea-pig taenia. Tetrodotoxin abolished the contraction or the contraction phase (but not the relaxation phase) of the biphasic response induced by neurotensin in the guinea-pig ileum. Atropine partially inhibited the neurotensin-induced contraction in the guinea-pig ileum. These results suggest that neurotensin acts on intestinal smooth muscle both directly (relaxation of the rat and guinea-pig ileum, and contraction of the guinea-pig taenia) and through a nerve-mediated, partly cholinergic, process (contraction of the guinea-pig ileum).     

Action of methylxanthines and imidazole on the contractility of the terminal ileum of the guinea pig

Methylxanthines (aminophylline and caffeine) and imidazole, substances with an opposite action on phosphodiesterase (PDE), were found to contract the terminal ileum and to potentiate nerve-mediated responses — contractions elicited by electrical stimulation (ES) at 3 Hz and 30 Hz. Imidazole-induced contractions which were partly reduced by atropine, potentiated both responses to ES to about the same extent, and enhanced contractility of the preparation to histamine and potassium. The action of imidazole on the terminal ileum could be related to its influence on PDE in the smooth muscle.The effects of aminophylline and caffeine were found to be more complex, possibly involving some mechanisms other than inhibition of PDE. They produced atropine-sensitive contractions of the terminal ileum, which were potentiated by physostigmine and strongly depressed by hemicholinium. In the presence of atropine, they potentiated ES-induced contractions, particularly those elicited by ES at 30 Hz, which are thought to be of adrenergic orig origin. Both actions appeared to be due to presynaptic effects—activation of cholinergic and adrenergic neurons in the intestinal wall, possibly by enhanced influx of calcium, and facilitated release of acetylcholine and noradrenaline. Aminophylline, in concentrations which potentiated nerve-mediated contractions elicited by ES, did not affect direct smooth muscle-contracting action of drugs. Higher concentrations of aminophylline, above 0.1 mM, were found to inhibit histamine- and noradrenaline-induced contractions presumbly due to inhibition of PDE in the smooth muscle and subsequent elevation of cAMP levels.     

D1 receptors play a major role in the dopamine modulation of mouse ileum contractility

Since the role of dopamine in the bowel motility is far from being clear, our aim was to analyse pharmacologically the effects of dopamine on mouse ileum contractility. Contractile activity of mouse ileum was examined in vitro as changes in isometric tension. Dopamine caused a concentration-dependent reduction of the spontaneous contraction amplitude of ileal muscle up to their complete disappearance. SCH-23390, D1 receptor antagonist, which per se increased basal tone and amplitude of spontaneous contractions, antagonized the responses to dopamine, whilst sulpiride or domperidone, D2 receptor antagonists, were without effects. The application of both D1 and D2 antagonists had additive effects. SKF-38393, D1 receptor agonist, mimicked dopamine-induced effects. Dopamine responses were insensitive to tetrodotoxin, atropine, nitric oxide synthase inhibitor or adenosine receptor antagonists, but they were reduced by adenylyl cyclase inhibition or apamin. Dopamine at a concentration which did not cause a significant reduction of phasic contractions inhibited the cholinergic contractions in response to field stimulation. SCH-23390 per se induced an increase of the neural cholinergic contraction and antagonized the dopamine effects, whilst sulpiride or domperidone did not. The application of D1 and D2 antagonists had additive effects. In conclusion, mouse ileum is under basal inhibitory control by dopamine, through D1 receptor activation, linked to adenylyl cyclase and activation of apamin-sensitive potassium channels. An agonistic interaction of the dopamine receptor subtypes in the regulation intestinal contractility has being also highlighted. This study would provide new insight on the pharmacology of the modulation of the gastrointestinal contractility by dopamine.     

The stimulant cathartic, emodin, contracts the rat isolated ileum by triggering release of endogenous acetylcholine

Anthraquinone stimulant cathartics, such as emodin, are believed to increase the rate of contraction of ileum tissue in vitro via multiple mechanisms. The aim of this study was to probe the effects of emodin on acetylcholine (ACh)-induced contraction of the rat isolated ileum preparation. 2 Ileal sections were incubated in Tyrode's solution and responses to methacholine, ACh and emodin obtained in the absence and presence of the muscarinic antagonist atropine and the choline uptake inhibitor hemicholinium (HC-3). Depletion of endogenous ACh in the presence of HC-3 was achieved by construction of an ACh dose-response curve, using exogenous ACh, prior to re-testing the effects of emodin in the presence of HC-3. 3 Emodin caused dose-dependent tissue contraction that was abolished by inclusion of atropine (1 microM) in the buffer. Atropine (1 microM) antagonized the response caused by methacholine. Incubation of tissues with HC-3 (1 and 10 microM) reduced the maximum response caused by emodin by 45% and 71% respectively, but had no effect on ACh-induced tissue contraction. These data suggest that, emodin causes contraction of the ileum by triggering the release of endogenous ACh which acts on muscarinic receptors to cause contraction of the rat isolated ileum preparation.     

Modulation of mouse gastrointestinal motility by allyl isothiocyanate, a constituent of cruciferous vegetables (Brassicaceae): evidence for TRPA1-independent effects

BACKGROUND AND PURPOSE

Allyl isothiocyanate (AITC, mustard oil), a constituent of many common cruciferous vegetables (Brassicaceae), activates transient receptor potential of ankyrin type-1 (TRPA1) channels, claimed to regulate gastrointestinal contractility. In this study, we have investigated the effect of AITC on intestinal motility.

EXPERIMENTAL APPROACH

Effects of AITC were investigated in vivo on upper gastrointestinal transit in mice and in mouse isolated ileum [contractions induced by electrical field stimulation (EFS), acetylcholine and spontaneous contractility]. The contractor activity of AITC was studied in mouse isolated colon. The ability of TRPA1 channel antagonists to block AITC-induced elevation of intracellular Ca²⁺[Ca²⁺]_i was assessed in HEK293 cells transfected with rat TRPA1 channels.

KEY RESULTS

AITC increased [Ca²⁺]_i in HEK293 cells, reduced ileal contractility (acetylcholine-, EFS-induced contractions and spontaneous contractility), but contracted the isolated colon. Gentamicin and camphor (non-selective TRPA1 channel antagonists), HC-030031 and AP18 (selective TRPA1 channel agonists) inhibited AITC-induced effects in HEK293 cells but not in the ileum or colon. AITC-induced contractions were reduced by tetrodotoxin and strongly reduced by nifedipine, cyclopiazonic acid and ryanodine. In vivo, AITC reduced (following i.p. administration) or increased (following intragastric administration) upper gastrointestinal transit in mice These effects were not affected by HC-030031.

CONCLUSION AND IMPLICATIONS

AITC, depending, in vitro, on the regions of gut examined and, in vivo, on the route of administration, exerted both stimulatory and inhibitory effects on intestinal motility, which were not sensitive to TRPA1 channel antagonists. The proposition that TRPA1 channels are the primary targets for AITC to induce contraction should be revised.     

A pharmacologic study on the histamine releasing effect of atracurium and other muscle relaxants in rat isolated ileum

In this study, the effects of histamine, antihistamines (terfenadine and mepyramine), 5-hydroxytryptamine, and muscle relaxants, atracurium, vecuronium and gallamine, on the tone and contractility of rat ileum were studied and compared in vitro. The aim of the present investigation was to measure, pharmacologically, the histamine releasing effect of muscle relaxants, e.g atracurium, vecuronium and gallamine, by comparing their contractile response in the absence and presence of antihistamines and comparing their mechanical responses with those produced by histamine and 5-hydroxytryptamine (5-HT). The results showed that the antihistamines, triludan(terfenadine) and mepyramine produced opposite effects in rat ileum. Terfenadine (0.1-20 microM) produced concentration-dependent contractions in the rat ileum, whereas mepyramine (0.1-10 microM) relaxed the muscle, e.g. by 1.2 g tension. Atracurium (0.5-500 microM), vecuronium (0.2-200 microM), and gallamine (0.1-7.0 microM) produced marked contractions (1.5-4.0 g tension) in rat ileum, and these contractions were markedly reduced by mepyramine (1.3 microM) or terfenadine (5 microM), implicating histamine release in the generation of these contractions. However, there was some residual contraction which was not blocked by mepyramine, but by 5-HT antagonist, methysergide (1 microM), indicating that a mechanism other than histamine release may be responsible for the residual contraction, i.e. release of other mediators such as 5-HT, prostaglandins, or calcium. 5-HT (0.5-500 microM) and histamine (0.5-500 microM) produced contractions in the rat ileum, but 5-HT was more effective than histamine in producing these contractions. Similarly, gall amine was more effective than atracurium and vecuronium in contracting the rat ileum.(ABSTRACT TRUNCATED AT 250 WORDS)     

小儿健脾膏整方及其单味药对大鼠离体胃、回肠平滑肌作用的比较研究

目的 观察比较小儿健脾膏整方及其单味药对大鼠离体胃、回肠平滑肌的作用,辨识该方中具有促胃肠动力的味药,为探讨其药效物质奠定基础。方法 用生物信号采集系统记录小儿健脾膏整方及其单味药对正常大鼠胃、回肠平滑肌收缩张力的变化,并比较其作用大小。结果 整方及其单味药对胃肌收缩的促进作用：整方 > 丁香 > 山楂 > 肉桂,白胡椒作用不显著;对回肠平滑肌的促进作用：丁香 > 整方 > 山楂,肉桂、白胡椒作用不显著;吴茱萸对胃、回肠收缩呈双向调节,小剂量促进,大剂量抑制。结论 小儿健脾膏整方对离体胃、回肠平滑肌收缩有促进作用;单味药中有明显促进作用的是丁香和山楂,吴茱萸呈双向调节作用;丁香和山楂是该方中促胃肠动力作用的主要味药。