Contractions Of Small Intestine Research Articles

Anti-Anemic and Anti-Dyspepsia Potential of Yogurt with Carao (Cassia grandis) in Rat Model

Iron deficiency anemia is a significant health problem in developing countries and this is rising, particularly in children and pregnant women. Several therapeutic properties have been attributed to Cassia grandis (carao), including the treatment against anemia, a laxative effect, and the reduction of bleeding. Yogurt is a vehicle for functional ingredients. As a result, this investigation aims to examine the application of Cassia grandis pulp as an anti-anemic and anti-dyspepsia agent in enriched yogurt. Carao pulp powder was added to milk at 0%, 0.5%, 1%, and 3% to produce yogurt. The bioavailability characteristics of iron deficiency anemia were analyzed in albino rats, which were studied for 4 weeks. Other groups of rats were used to set up the dyspepsia model by being fed a high-fat and high-calorie diet. Intestinal propulsion rate, gastric emptying rate, small intestinal contraction, motilin levels, and intestinal muscle tension were analyzed in rats with dyspepsia. Yogurt with 3% carao pulp powder restored ferritin, hemoglobin, total protein and iron at the end of the 4-week feeding period, with significant competition revealed in calcium and zinc absorbance. Furthermore, yogurt with 3% carao pulp powder improved intestinal propulsion rate, gastric emptying rate, small intestinal contraction, motilin levels, and intestinal muscle tension in dyspepsia rats. Carao can be recommended as an anti-anemia supplement in yogurt fortification.

Effect of cholecystokinin on small intestinal motility in suncus murinus

In a fasting gastrointestinal tract, a characteristic cyclical rhythmic migrating motor complex (MMC) occur that comprises of three phases: I, II, and III. Among these, phase III contractions propagate from the stomach to the lower intestine in mammals, including humans, dogs, and Suncus murinus (suncus). Apart from the phase III of MMC propagating from the stomach, during the gastric phase II, small intestine-originated strong contractions propagate to the lower small intestine; however, the mechanism of contractions originating in the small intestine has not been clarified. In this study, we aimed to elucidate the role of cholecystokinin (CCK) in small intestinal motility. Administration of sulfated CCK-8 in phase I induced phase II-like contractions in the small intestine, which lasted for approximately 10–20 min and then returned to the baseline, while no change was observed in the stomach. Contractions of small intestine induced by CCK-8 were abolished by lorglumide, a CCK1 receptor antagonist. Gastrin, a ligand for the CCK2 receptor, evoked strong contractions in the stomach, but did not induce contractions in the small intestine. To examine the effect of endogenous CCK on contractions of small intestinal origin, lorglumide was administered during phase II. However, there was no change in the duodenal motility pattern, and strong contractions of small intestinal origin were not abolished by treatment with lorglumide. These results suggest that exogenous CCK stimulates contractions of small intestine via CCK1 receptors, whereas endogenous CCK is not involved in the strong contractions of small intestinal origin.

Enhanced Store-Operated Ca2+ Signal of Small Intestinal Smooth Muscle Cells Accelerates Small Bowel Transit Speed in Type 1 Diabetic Mouse.

Aims: The underlying mechanism of diabetic enteropathy, a common complication of type 1 diabetes, remains unclear. Store-operated Ca2+ entry (SOCE) is a ubiquitous type of Ca2+ influx involved in various cellular functions. Here, we show that SOCE-related stromal interaction molecule 1 (STIM1) and Orai1 participate in inappropriate cellular Ca2+ homeostasis, augmenting agonist-induced small intestinal smooth muscle contraction and small bowel transit speed in a mouse model of type 1 diabetes.Methods and Results: We used small interfering (si)RNA to suppress STIM1 and Orai1 proteins, and employed intracellular Ca2+, small intestinal contraction and intestinal transit speed measurement to investigate the functional change. We found that SOCE activity and Orai1 and STIM1 expression levels of small intestinal smooth muscle were significantly increased in cells cultured in high glucose medium or in diabetic mice. Gastrointestinal transit speed and SOCE-mediated contractions were markedly increased in diabetic mice; Knocking down Orai1 or STIM1 with siRNA rescued both alterations in diabetic mice. However, the Orai1-large conductance Ca2+-activated K+ (BKCa) channel interaction was decreased in diabetic mice, and suppressing Orai1 expression or inhibiting the BKCa channel increased agonist-induced small intestinal contractions in normal mice.Conclusion: We concluded that the increased SOCE caused by excessive STIM1 and Orai1 expression and decreased Orai1-BKCa interaction augmented small intestinal smooth muscle contraction and accelerated small bowel transit speed in diabetic mice. This finding demonstrates a pathological role for SOCE in diabetic enteropathy and provides a potential therapeutic target for diabetic enteropathy.

A Cannabinoid-1 Receptor Antagonist MJ08 with Different Effects in Stomach and Small Intestine.

Background:To investigate the inverse agonistic effect of a novel type 1 cannabinoid (CB1) receptor antagonist, MJ08, on the gastrointestinal tract (GIT).Methods: In vivo, carbon propulsion within the stomach of mice was undertaken to investigate the effects of MJ08. In vitro, the effects of MJ08 were investigated on the contraction of smooth muscle on the isolated gastric fundus, gastric body, duodenum, jejunum, and ileum.Results:Western blotting results showed that MJ08 (0.62 mg/kg body weight) reversed WIN55,212-2 (1.0 mg/kg)-induced reduction of carbon transit. MJ08 (1.25, 2.5 mg/kg) stimulated carbon transit dose dependently, demonstrating an inverse agonistic effect. In vitro experiments showed that the expression of MJ08 increased the contraction of small intestine, and that its inverse agonistic effect was significantly stronger than that of SR141716A, but no effect was noted on the gastric body. Western blotting showed that the MJ08 increased the expression of CB1 receptor in different GIT segments.Conclusion:MJ08 is not only an antagonist but also an inverse agonist of the CB1 receptor. MJ08 and SR141716A can enhance motility in the small intestine and increase the expression of CB1 receptor in the small intestine.

Suppression of mICAT in Mouse Small Intestinal Myocytes by General Anaesthetic Ketamine and its Recovery by TRPC4 Agonist (-)-englerin A.

A better understanding of the negative impact of general anesthetics on gastrointestinal motility requires thorough knowledge of their molecular targets. In this respect the muscarinic cationic current (mICAT carried mainly via TRPC4 channels) that initiates cholinergic excitation-contraction coupling in the gut is of special interest. Here we aimed to characterize the effects of one of the most commonly used “dissociative anesthetics”, ketamine, on mICAT. Patch-clamp and tensiometry techniques were used to investigate the mechanisms of the inhibitory effects of ketamine on mICAT in single mouse ileal myocytes, as well as on intestinal motility. Ketamine (100 µM) strongly inhibited both carbachol- and GTPγS-induced mICAT. The inhibition was slow (time constant of about 1 min) and practically irreversible. It was associated with altered voltage dependence and kinetics of mICAT. In functional tests, ketamine suppressed both spontaneous and carbachol-induced contractions of small intestine. Importantly, inhibited by ketamine mICAT could be restored by direct TRPC4 agonist (-)-englerin A. We identified mICAT as a novel target for ketamine. Signal transduction leading to TRPC4 channel opening is disrupted by ketamine mainly downstream of muscarinic receptor activation, but does not involve TRPC4 per se. Direct TRPC4 agonists may be used for the correction of gastrointestinal disorders provoked by general anesthesia.

Identification of pheasant ghrelin and motilin and their actions on contractility of the isolated gastrointestinal tract

Motilin and ghrelin were identified in the pheasant by molecular cloning, and the actions of both peptides on the contractility of gastrointestinal (GI) strips were examined in vitro. Molecular cloning indicated that the deduced amino acid sequences of the pheasant motilin and ghrelin were a 22-amino acid peptide, FVPFFTQSDIQKMQEKERIKGQ, and a 26-amino acid peptide, GSSFLSPAYKNIQQQKDTRKPTGRLH, respectively. In in vitro studies using pheasant GI strips, chicken motilin caused contraction of the proventriculus and small intestine, whereas the crop and colon were insensitive. Human motilin, but not erythromycin, caused contraction of small intestine. Chicken motilin-induced contractions in the proventriculus and ileum were not inhibited by a mammalian motilin receptor antagonist, GM109. Neither atropine (a cholinergic receptor antagonist) nor tetrodotoxin (a neuron blocker) inhibited the responses of chicken motilin in the ileum but both drugs decreased the responses to motilin in the proventriculus, suggesting that the contractile mechanisms of motilin in the proventriculus was neurogenic, different from that of the small intestine (myogenic). On the other hand, chicken and quail ghrelin did not cause contraction in any regions of pheasant GI tract. Since interaction of ghrelin and motilin has been reported in the house musk shrew, interaction of two peptides was examined. The chicken motilin-induced contractions were not modified by ghrelin, and ghrelin also did not cause any contraction under the presence of motilin, suggesting the absence of interaction in both peptides. In conclusion, both the motilin system and ghrelin system are present in the pheasant. Regulation of GI motility by motilin might be common in avian species. However, absence of ghrelin actions in any GI regions suggests the avian species-related difference in regulation of GI contractility by ghrelin.

Effect of Yogurt on Gastrointestinal Motility of Dyspepsia Mice

With the development of the food industry and the improvement of the living standard, people’s diet structure has changed gradually. Excessive diet with high calorie and high protein could cause dyspepsia. Aim of our study is to discuss the effect of yogurt on gastrointestinal motility of dyspepsia mice. Mice were randomly divided into four groups: normal group, model group, Chinese medical group (Drug group), and yogurt group. The mice of normal group were given ordinary feed, the rest of groups were given high protein and high calorie feed and administered through gastric intubation with 52% milk solution to establish dyspeptic model from day 1 to 4. the gastric emptying rate, intestinal propulsion rate, intestinal muscle tension, small intestinal contraction frequency and motilin were measured. Compared with the normal group, the gastric emptying rate, small intestinal propulsion rate, small intestine muscle tension, the small intestine contraction frequency and the motilin concentration were decreased in the model group, Compared with the model group, the intestine muscle tension in the yogurt group was increased, the difference has statistical significance(p<0.05), in addition, the gastric emptying rate in yogurt group was increased(p<0.05),the small intestine contraction frequency and the motilin of yogurt group were increased.Yogurt could improve gastrointestinal motility of dyspepsia mice.

Azithromycin Induces Migrating Motor Complexes in Pediatric Patients Undergoing Antroduodenal Motility Studies.

Erythromycin (ERY) is used in the treatment of gastroparesis; however, this medication is associated with serious side effects, such as cardiac arrhythmias and consequent cardiorespiratory arrest. Azithromycin (AZM) has been suggested as an alternative to ERY as a result of its improved safety profile. Intravenous ERY (1 mg/kg) is administered during antroduodenal motility studies to induce migrating motor complexes (MMCs), the presence or absence of which helps diagnose motility disorders like gastroparesis and gastrointestinal dysmotility. However, there are no pediatric studies comparing the effects of AZM and ERY on antroduodenal pressure profiles. The goal of this study is to determine if AZM is comparable in inducing MMCs in pediatric patients undergoing antroduodenal motility studies. We performed a retrospective chart analysis of gastric and small bowel manometric data in 2 adolescent patients, both age 15 years, who were given AZM (1 mg/kg) during antroduodenal motility studies. The pressure profiles obtained during motility studies were compared to those of patients of similar age and symptomology who were given the standard intravenous ERY dose during motility studies. We then compared the total duration of effect, mean amplitude of contractions, number of cycles per minute, and duration of highest antral and duodenal contractions. Intravenous AZM induces migrating motor contractions in the stomach followed by contractions in the small intestine. The mean amplitude of the stomach contractions was 259 mm Hg in patients who received AZM vs 241 mm Hg in patients who received ERY. The mean amplitude of small intestinal MMCs was 68 mm Hg in patients who received AZI and 72 mm Hg in patients who received ERY. Additionally, the frequency and duration of stomach and small intestinal contractions were also similar in the 2 groups. Intravenous AZM has similar prokinetic effects to intravenous ERY. Our study suggests that AZM is a suitable alternative to ERY in inducing MMCs without the concerning side effects related to ERY and may potentially be used in the management of gastroparesis and other small bowel motility disorders. However, larger prospective studies are required to better understand the long-term efficacy of AZM.

Effects of the Venom of the Brown Bullhead Catfish (Ameiurus Nebulosus) on Isolated Smooth Muscles

Aqueous extract of the spines of the brown bullhead catfish (Ameiurus nebulosus Lesueur, 1819) caused contraction of the guinea-pig small intestine in vitro, a widely-used preparation in pharmacology. The action is dependent on extracellular Ca2+, and probably takes place on the smooth muscle cells. Mouse gastrointestinal preparations were also contracted by the extract. Stings by the spines of this fish species causes a painful sensation in man. We tested the effect of an extract of spines in isolated organ experiments on innervated smooth muscle preparations. In the guinea-pig ileum, the response to the extract was abolished by the Ca2+-channel blocker nifedipine, but only slightly reduced by atropine (a muscarine receptor antagonist) or tetrodotoxin (TTX; a blocker axonal conduction) or antagonists for P2X purinoceptors. Blocking of serotonin or histamine H1 receptors, tachykinin NK1 receptors, functional impairment of capsaicin-sensitive sensory nerve endings or inhibition of cyclo-oxygenases failed to infuence the contractile effect of the extract. No inhibitory action of the extract was detected on the ileum subject to electrical motor nerve stimulation.

Ginger Extract and [6]-Gingerol Inhibit Contraction of Rat Entire Small Intestine.

This study aims to investigate the effect of oral administration and the direct action of ginger extract or [6]-gingerol on small intestinal contractility. The direct effect of 10 minutes preincubation of ginger ethanolic extract (10, 100 and 300 μg/mL) or [6]-gingerol (1, 30, and 100 μM) on 0.01 to 30 μM ACh-induced contractions of all parts of the small intestine isolated from normal rats was investigated using the organ bath technique. For in vivo study, the rats were orally administered with extract (10, 20, and 100 mg/kg/d) or [6]-gingerol (2 mg/kg/d) for 7 days, followed by determining the contractile responses to ACh of rat isolated duodenum, jejunum, and ileum and their histology were assessed. Direct application of the extract or [6]-gingerol attenuated ACh-induced contractions in each small intestinal segment, E max was reduced by 40% to 80%, while EC50 increased 3- to 8-fold from control. Similarly, in the in vivo study ACh-induced contractions were reduced in all parts of the small intestine isolated from rats orally treated with ginger extract (20 and 100 mg/kg/d) or [6]-gingerol (2 mg/kg/d). E max decreased 15% to 30%, while EC50 increased 1- to 3-fold compared to control. No discernable changes in the histology of intestinal segments were detectable. Thus, the results support the clinical application of ginger for disorders of gastrointestinal motility.

The phase response and state space of slow wave contractions in the small intestine.

What is the central question of this study? What are the dynamical rules governing interstitial cell of Cajal (ICC)-generated slow wave contractions in the small intestine, as reflected in their phase response curve and state space? What is the main finding and its importance? The phase response curve has a region of phase advance surrounding a phase delay peak. This pattern is important in generating a stable synchrony within the ICC network and is related to the state space of the ICC; in particular, the phase delay peak corresponds to the unstable equilibrium point that threads the ICC's limit cycle. Interstitial cells of Cajal (ICCs) generate electrical oscillations in the gut. Synchronization of the ICC population is required for generation of coherent electrical waves ('slow waves') that cause muscular contraction and thereby move gut content. The phase response curve (PRC) is an experimental measure of the dynamical rules governing a population of oscillators that determine their synchrony and gives an experimental window onto the state space of the oscillator, its dynamical landscape. We measured the PRC of slow wave contractions in the mouse small intestine by the novel combination of diameter mapping and single pulse electrical field stimulation. Phase change (τ) was measured as a function of old phase (ϕ) and distance from the stimulation electrode (d). Plots of τ(ϕ, d) showed an arrowhead-shaped region of phase advance enclosing at its base a phase delay peak. The phase change mirrored the perturbed pattern of contraction waves in response to a pulse. The (ϕ, d) plane is the surface of a displacement tube extending from the limit cycle through state space. To visualize the state space vector field on this tube, latent phase (ϕlat ) was calculated from τ. At the transition from advance to delay, isochrons made boomerang turns before tightening and winding around the phase delay peak corresponding to the unstable equilibrium point that threads the limit cycle. This isochron foliation had previously been observed in oscillator models such as the Fitzhugh-Nagumo but has not been demonstrated experimentally. The spatial extension of the PRC afforded by diameter mapping allows a better understanding of the dynamical properties of ICCs and how they synchronize as a population.

Extraction and processing of videocapsule data to detect and measure the presence of villous atrophy in celiac disease patients

BackgroundVideocapsule endoscopy is a relative new method to analyze the gastrointestinal tract for the presence of pathologic features. It is of relevance to detect villous atrophy in the small bowel, which is a defining symptom of celiac disease. MethodIn this tutorial, methods to extract and process videocapsule endoscopy data are elucidated. The algorithms, computer code, and paradigms to analyze image series are described in detail. The topics covered include extraction of data, analysis of texture, eigenanalysis, spectral analysis, three-dimensional projection, and estimation of motility. The basic paradigms to implement these processes are provided. ResultsExamples of successful quantitative analysis implementations for selected untreated celiac disease patients with villous atrophy versus control patients with normal villi were illustrated. Based on the implementations, it was evident that celiac patients tended to have a rougher small intestinal texture as compared with control patients. From three-dimensional projection, celiac patients exhibited larger surface protrusions emanating from the small intestinal mucosa, which may represent clumps of atrophied villi. The periodicity of small intestinal contractions tends to be slower when villous atrophy is present, and the estimated degree of motility is reduced as compared with control image series. Basis image construction suggested that fissuring and mottling of the mucosal surface is predominant in untreated celiac patients, and mostly absent in controls. ConclusionsImplementation of computerized methods, as described in this tutorial, will likely be useful for the automated detection and measurement of villous atrophy, and to map its extent along the small intestine of celiac patients.

Modeling the contractile characteristics of smooth muscle from the porcine small intestine

Defining the physiological condition of smooth muscle in more detail is the key to understanding the disease mechanism of smooth muscle defective diseases and the development of novel medical devices to help patients with these diseases. Although previous studies have detailed the physiological condition of smooth muscle contraction in gastrointestinal tracts, the precise characteristics of muscle contraction before or after stimulation have yet to be determined due to a lack of accuracy or inconsistency. Here, we obtain the passive characteristic parameters of smooth muscle and the active characteristic parameters of smooth muscle contraction from the porcine small intestine. To obtain the passive characteristic parameters of smooth muscle, we measured tensile strength in the porcine small intestine. The maximum repulsive force, 0.702 N, was measured in tensile tests. To estimate the active characteristic parameters of smooth muscle, we stimulated with acetylcholine and measured the isometric and isotonic contractions in the porcine small intestine. The maximum myotility, 12.35 mN, was obtained in isometric experiments, and the maximum velocity of muscular contraction, 0.4476 mm/min, was obtained in isotonic experiments. By applying the data acquired through experiments to the modified Hill-type muscle model, the active and passive characteristics of the porcine small intestine were schematized. Our model of smooth muscle from the porcine small intestine may be helpful for developing novel medical devices and understanding the physiology of smooth muscle in the porcine small intestine.

Inhibitory Effects and Sympathetic Mechanisms of Distension in the Distal Organs on Small Bowel Motility and Slow Waves in Canine.

Rectal distension (RD) is known to induce intestinal dysmotility. Few studies were performed to compare effects of RD, colon distension (CD) and duodenal distension (DD) on small bowel motility. This study aimed to investigate effects and underlying mechanisms of distensions in these regions on intestinal motility and slow waves. Eight dogs chronically implanted with a duodenal fistula, a proximal colon fistula, and intestinal serosal electrodes were studied in six sessions: control, RD, CD, DD, RD+guanethidine, and CD+guanethidine. Postprandial intestinal contractions and slow waves were recorded for the assessment of intestinal motility. The electrocardiogram was recorded for the assessment of autonomic functions. (1) Isobaric RD and CD suppressed intestinal contractions (contractile index: 6.0±0.4 with RD vs. 9.9±0.9 at baseline, P=0.001, 5.3±0.2 with CD vs. 7.7±0.8 at baseline, P=0.008). Guanethidine at 3mg/kg iv was able to partially block the effects. (2) RD and CD reduced the percentage of normal intestinal slow waves from 92.1±2.8 to 64.2±3.4% (P<0.001) and from 90±2.7 to 69.2±3.7% (P=0.01), respectively. Guanethidine could eliminate these inhibitory effects. (3) DD did not induce any changes in small intestinal contractions and slow waves (P>0.05). (4) The spectral analysis of the heart rate variability showed that both RD and CD increased sympathetic activity (LF) and reduced vagal activity (HF) (P<0.05). Isobaric RD and CD could inhibit postprandial intestinal motility and impair intestinal slow waves, which were mediated via the sympathetic pathway. However, DD at a site proximal to the measurement site did not seem to impair small intestinal contractions or slow waves.

The effect of temperature changes on in vitro slow wave activity in the equine ileum.

Slow waves are rhythmic pacemaker currents generated by the gastrointestinal pacemaker cells, the interstitial cells of Cajal, and represent the rate-limiting step for small intestinal smooth muscle contractions. Therefore, factors that affect slow wave activity may also influence contractile activity. It is not known how temperature changes may influence slow wave activity in the horse. This could be of relevance during colic surgery if cooling of exposed intestine resulted in reduced slow wave activity potentially exacerbating post operative ileus. To evaluate the effect of temperature changes on in vitro slow wave activity of normal equine ileum using intracellular recording techniques. In vitro experimental study. A segment of ileum was collected immediately following euthanasia from 9 horses for reasons unrelated to the gastrointestinal tract. Intracellular recordings of membrane potentials were made from individual smooth muscle cells. The temperature of the tissue bath was altered during the course of each experiment across a range of 27-41°C. All data were recorded and stored using a computer-interfaced acquisition system. A software package was used to analyse slow wave frequency, duration, amplitude and resting membrane potential. In all 9 horses, slow wave frequency was highly temperature sensitive and approximately linearly related to the temperature over the range studied, increasing by 0.5 cycles/min for each 1°C increase in temperature (P<0.001). The initial slow wave frequency resumed when the temperature was returned to 37°C. The recovery time appeared to be directly related to the duration for which the temperature had been changed. Slow wave frequency in the equine ileum is highly temperature sensitive. As post operative ileus is a major cause of morbidity and mortality in the horse, the negative effect of lower temperatures on slow waves, and therefore contractile activity, should be considered.

A review of mixing and propulsion of chyme in the small intestine: fresh insights from new methods.

The small intestine is a convoluted flexible tube of inconstant form and capacity through which chyme is propelled and mixed by varying patterns of contraction. These inconstancies have prevented quantitative comparisons of the manner in which contractile activity engenders mixing of contained chyme. Recent quantitative work based on spatiotemporal mapping of intestinal contractions, macro- and micro-rheology, particle image velocimetry and real-time modelling has provided new insights into this process. Evidence indicates that the speeds and patterns of the various types of small intestinal contraction are insufficient to secure optimal mixing and enzymatic digestion over a minimal length of intestine. Hence particulate substrates and soluble nutrients become dispersed along the length of the lumen. Mixing within the lumen is not turbulent but results from localised folding and kneading of the contents by contractions but is augmented by the inconstant spatial disposition of the contractions and their component contractile processes. The latter include inconstancies in the sites of commencement and the directions of propagation of contraction in component groups of smooth muscle cells and in the coordination of the radial and circular components of smooth muscle contraction. Evidence suggests there is ongoing augmentation of mixing at the periphery of the lumen, during both the post-prandial and inter-meal periods, to promote flow around and between adjacent villi. This results largely from folding of the relatively inelastic mucosa during repeated radial and longitudinal muscular contraction, causing chyme to be displaced by periodic crowding and separation of the tips of the relatively rigid villi. Further, micro-rheological studies indicate that such peripheral mixing may extend to the apices of enterocytes owing to discontinuities in the mobile mucus layer that covers the ileal mucosa.

Prokinetic effects of mirtazapine on gastrointestinal transit

Mirtazapine is a noradrenergic and specific serotonergic antidepressant. The aim of this study was to investigate the effects of mirtazapine on gastrointestinal motility in dogs, including solid gastric emptying, antral and small intestinal contractions, and small intestinal and colonic transit. Six dogs were implanted with two cannulas located at the duodenum and the ascending colon; another six dogs were implanted with gastric cannula 6 cm proximal to the pylorus. Mirtazapine 45 mg was administered orally 90 min before the study. We found that 1) Mirtazapine accelerated gastric emptying during the entire 3 h in normal dogs (P < 0.04) and accelerated delayed gastric emptying induced by rectal distention (P < 0.04). 2) Mirtazapine restored impaired gastric tone and accommodation induced by rectal distention (P < 0.05). 3) No significant changes were noted in small intestinal contractions or transit with mirtazapine (P > 0.1). 4) Mirtazapine accelerated colonic transit at 2 and 4 h but not 6 h. The geometric center was increased from 1.9 ± 0.6 to 3.0 ± 0.5 and 3.9 ± 0.5 to 4.7 ± 0.1 at 2 and 4 h respectively (P = 0.04 vs. corresponding control). In conclusion, mirtazapine improves gastric emptying in healthy dogs and normalizes rectal distention-induced delay in gastric emptying and accelerates colon but not small intestinal transit in healthy dogs. Clinical studies are warranted to assess the effects of mirtazapine on gastrointestinal motility and sensory functions in patients with functional gastrointestinal diseases.

Deletion ofGpr128results in weight loss and increased intestinal contraction frequency

To generate a Gpr128 gene knockout mouse model and to investigate its phenotypes and the biological function of the Gpr128 gene. Bacterial artificial chromosome-retrieval methods were used for constructing the targeting vector. Using homologous recombination and microinjection technology, a Gpr128 knockout mouse model on a mixed 129/BL6 background was generated. The mice were genotyped by polymerase chain reaction (PCR) analysis of tail DNA and fed a standard laboratory chow diet. Animals of both sexes were used, and the phenotypes were assessed by histological, biochemical, molecular and physiological analyses. Semi-quantitative reverse transcription-PCR and Northern blotting were used to determine the tissue distribution of Gpr128 mRNA. Beginning at the age of 4 wk, body weights were recorded every 4 wk. Food, feces, blood and organ samples were collected to analyze food consumption, fecal quantity, organ weight and constituents of the blood and plasma. A Trendelenburg preparation was utilized to examine intestinal motility in wild-type (WT) and Gpr128(-/-) mice at the age of 8 and 32 wk. Gpr128 mRNA was highly and exclusively detected in the intestinal tissues. Targeted deletion of Gpr128 in adult mice resulted in reduced body weight gain, and mutant mice exhibited an increased frequency of peristaltic contraction and slow wave potential of the small intestine. The Gpr128(+/+) mice gained more weight on average than the Gpr128(-/-) mice since 24 wk, being 30.81 ± 2.84 g and 25.74 ± 4.50 g, respectively (n = 10, P < 0.01). The frequency of small intestinal peristaltic contraction was increased in Gpr128(-/-) mice. At the age of 8 wk, the frequency of peristalsis with an intraluminal pressure of 3 cmH2O was 6.6 ± 2.3 peristalsis/15 min in Gpr128(-/-) intestine (n = 5) vs 2.6 ± 1.7 peristalsis/15 min in WT intestine (n = 5, P < 0.05). At the age of 32 wk, the frequency of peristaltic contraction with an intraluminal pressure of 2 and 3 cmH2O was 4.6 ± 2.3 and 3.1 ± 0.8 peristalsis/15 min in WT mice (n = 8), whereas in Gpr128(-/-) mice (n = 8) the frequency of contraction was 8.3 ± 3.0 and 7.4 ± 3.1 peristalsis/15 min, respectively (2 cmH2O: P < 0.05 vs WT; 3 cmH2O: P < 0.01 vs WT). The frequency of slow wave potential in Gpr128(-/-) intestine (35.8 ± 4.3, 36.4 ± 4.2 and 37.1 ± 4.8/min with an intraluminal pressure of 1, 2 and 3 cmH2O, n = 8) was also higher than in WT intestine (30.6 ± 4.2, 31.4 ± 3.9 and 31.9 ± 4.5/min, n = 8, P < 0.05). We have generated a mouse model with a targeted deletion of Gpr128 and found reduced body weight and increased intestinal contraction frequency in this animal model.

The effect of dietary supplementation of nitric oxide donor and inhibitor on nNOS expression in and motility of the small intestine of broilers

We investigated the effect of dietary supplementation of sodium nitroprusside (SNP), a nitric oxide (NO) donor, and N-nitro-L-arginine methyl ester (L-NAME), a NO inhibitor, on neuronal nitric oxide synthase (nNOS) expression in and motility of small intestinum in broilers. A total of 560, one-day-old Ross 308 hybrid mixed sex broiler chicks were divided randomly into one control and seven treatment groups for a 42 day feeding trial including starter phase (0–21 days) and grower phase (22–42 days). The control group was fed a basal diet and the experimental groups were the fed basal diet supplemented with 25, 50, 100 and 200 mg/kg SNP and 25, 50 or 100 mg/kg L-NAME. Ten chickens from each group were sacrificed to collect samples on days 21 and 42. The expression patterns of nNOS immunoreactivity in nerve fibers were determined by immunohistochemistry. In the contractility studies, longitudinal isolated strips of duodenum, jejunum and ileum were treated with 10−5 M L-arginine and 10−4 M SNP. Immunohistochemistry revealed that nNOS expression was not detectable in the duodenum or ileum of either the control or experimental groups. On the other hand, nNOS immunoreactivity in the jejunum control group showed a strong reaction on day 21, but the reaction was weak on day 42. nNOS expression clearly was suppressed on day 21 by the diet supplemented with L-NAME, while the diet supplemented with SNP stimulated nNOS expression on day 21. Contractility experiments revealed that spontaneous contractility of isolated strips of duodenum, jejunum and ileum showed no significant difference among groups. Spontaneous contractions of all strips were inhibited by L-arginine and SNP in all groups. The percentage inhibition rate of spontaneous contractions of jejunum application on days 21 and 42 after L-arginine decreased in the group supplemented with 100 mg/kg L-NAME. The percentage inhibition rate on day 21 after SNP application decreased in both groups that received 50 and 100 mg/kg L-NAME. We demonstrated the expression pattern of nNOS in nerve fibers in jejunum of broiler chickens. Contractility studies revealed that the NOS-NO pathway may play a role in smooth muscle contraction of small intestine of chickens. Feeding strategies that supplement NO donor and NO inhibitor can be of physiological importance to small intestine motility owing to alteration of nNOS expression in the jejunum.

Peroxide-induced effects on spontaneous contraction of murine small intestine: Lack of inhibition by antioxidants

Peroxide-induced effects on spontaneous contraction of murine small intestine: Lack of inhibition by antioxidants