Characteristics of the motor function of the proximal segment of the gastrointestinal tract

Dynamics of the solid carbohydrate food evacuation from the duodenum has been determined in chronic experiments on dogs using modified technique for multiple drainage of intestinal fistulas. It is established that dynamics of the duodenal chyme emptying depends on the absolute quantity of the stomach-evacuated food and includes three phases: increase in the evacuation rate, exponential phase and that of accelerated evacuation. The highest rate of the duodenal contents is observed in the period from the 90th to 210th minute after food intake, the lowest one--at the end of the digestive cycle. A conclusion is made concerning the high degree of coordination of the evacuatory stomach and duodenum function.     

Small bowel motility and colonic transit are altered in dogs with moderate renal failure

Although gastrointestinal complications are common in patients with renal disease, the effects of renal dysfunction on bowel motility and gut transit times are not well known. We assessed gastrointestinal electromyographic activity, gastric emptying rate, orocolonic transit time, oroanal transit time, and xylose absorption before and after surgically inducing a 66% decrease in glomerular filtration rate in dogs. Moderate renal failure induced no gross or microscopic gastrointestinal lesions but caused a 16-42% increase in gastrointestinal motility indexes. We found a 24% decrease in the propagation velocity of the myoelectrical migrating complex in the duodenojejunal segment, a 30% decrease in phase I duration in duodenal and jejunal regions, a 20% increase in the total irregular electrical activity of the small intestine, and a 22% increase in duration of the meal response in the duodenum and jejunum. Renal failure did not change xylose absorption, gastric emptying rate, and orocolonic transit time but decreased colonic transit time by 38%. The mean weight of feces was increased. These results indicate that moderate renal failure alters duodenojejunal motility and decreases colonic transit time.     

Mechanical factors regulating gastric emptying examined by the effects of exogenous cholecystokinin and secretin on canine gastroduodenal motility

The aim of this study was to elucidate the variables of gastroduodenal motility determining gastric emptying. For this purpose the effects of exogenous cholecystokinin, secretin, and gastric inhibitory polypeptide on motility and gastric emptying were studied during a meal. Motility was measured with extraluminal strain gage force transducers and induction coils in unanaesthetized dogs. The pyloric diameter and the duodenal lumen were evaluated from radiographs. Gastric emptying of an acaloric cellulose meal was determined radiographically. When compared with control infusion of saline, cholecystokinin (1.7 Ivy units X kg-1 X h-1) and secretin (1.7 clinical units X kg-1 X h-1) delayed gastric emptying and diminished the force of the antral contractions, the force and frequency of the duodenal contractions, and opening of the pylorus. The contractile patterns of the duodenum were changed from propulsive to segmenting activity. Cholecystokinin additionally diminished the duodenal lumen. In contrast, gastric inhibitory polypeptide (1.5 microgram X kg-1 X h-1) did not influence gastroduodenal motility and gastric emptying. It is concluded that the motility parameters that were significantly altered by cholecystokinin and secretin are involved in the control of gastric emptying, while other parameters that remained unchanged play a minor role in the regulating process.     

Expression of 5-HT3 receptors by extrinsic duodenal afferents contribute to intestinal inhibition of gastric emptying

Intestinal perfusion with carbohydrates inhibits gastric emptying via vagal and spinal capsaicin-sensitive afferent pathways. The aim of the present study was to determine the role of 1) 5-hydroxytryptamine (5-HT)(3) receptors (5-HT(3)R) in mediating glucose-induced inhibition of gastric emptying and 2) 5-HT(3)R expression in vagal and spinal afferents in innervating the duodenum. In awake rats fitted with gastric and duodenal cannulas, perfusion of the duodenum with glucose (50 and 100 mg) inhibited gastric emptying. Intestinal perfusion of mannitol inhibited gastric emptying only at the highest concentration (990 mosm/kgH(2)O). Pretreatment with the 5-HT(3)R antagonist tropisetron abolished both glucose- and mannitol-induced inhibition of gastric emptying. Retrograde labeling of visceral afferents by injection of dextran-conjugated Texas Red into the duodenal wall was used to identify extrinsic primary afferents. Immunoreactivity for 5-HT(3)R, visualized with an antibody directed to the COOH terminus of the rat 5-HT(3)R, was found in >80% of duodenal vagal and spinal afferents. These results show that duodenal extrinsic afferents express 5-HT(3)R and that the receptor mediates specific glucose-induced inhibition of gastric emptying. These findings support the hypothesis that enterochromaffin cells in the intestinal mucosa release 5-HT in response to glucose, which activates 5-HT(3)R on afferent nerve terminals to evoke reflex changes in gastric motility. The primary glucose sensors of the intestine may be mucosal enterochromaffin cells.     

The role of Treitz' ligament in regulating the evacuation of solid food from the duodenum

In the chronic experiments on dogs by means of modified method of multiple drainage of the intestinal fistulas, the effect of the Treitz ligament transection on dynamics of solid carbohydrate food evacuation from the duodenum was studied. It was established that in the norm, evacuation from the duodenum was submitted to exponential law and depended on absolute quantity of food evacuated from the stomach. After the Treitz ligament transection, the evacuation through intestine had a non-exponential character. The operation led to disturbance in co-ordination between evacuatory function of the stomach and that of duodenum, and also had the depressive effect on intestinal emptying. The conclusion is made of the functional role of the Treitz ligament as active regulator of solid food evacuation from the duodenum.     

5-Hydroxytryptophan modulates postprandial motor patterns of canine proximal small intestine

The aim of the study was to clarify whether 5-hydroxytryptophan (5-HTP) stimulates the postprandial motor pattern of the duodenum in a similar way as that of the adjacent jejunal segment in dogs. Computerized analysis of motor patterns recorded by closely spaced strain gauges focused on the temporal and spatial distribution of the contractions. Results indicate that 5-HTP increased the incidence and the length of the spread of contraction waves after both an acaloric and a nutrient meal in the duodenum as well as in the adjacent jejunal segment. Effects were more pronounced after the nutrient than after the acaloric meal. After the nutrient meal, but not after the acaloric meal, 5-HTP additionally enhanced the number of both duodenal and jejunal contractions per minute and increased the force of duodenal contractions. The acaloric meal induced significant differences in the motor patterns between the duodenum and the adjacent jejunum. 5-HTP abolished these differences owing to a relatively stronger stimulation of duodenal motility. 5-HTP did not affect gastric emptying of both meals. We conclude (i) that 5-HTP is a potent stimulator of propagated contractions both in the duodenum and the adjacent jejunal segment and (ii) that intestinal motor patterns can be regulated independently of gastric emptying.     

A quantitative study on the myenteric plexus of the distal end of the duodenum and the proximal part of the jejunum

4 necropsy specimens taken from adult individuals were used in order to estimate the density of nerve cell bodies of the myenteric plexus in the last distal 5 cm of the duodenum and the proximal 5 cm of the jejunum (including the duodenojejunal flexure), that were subdivided into parts of approximately 1 cm and stained by Giemsa's method according to Barbosa (1970). Except for the first 2 parts, an increase of the neuron number was observed toward the duodenojejunal flexure, the greatest being at this point, and then decreasing progressively. The first duodenal parts, which corresponds approximately to the intersection of the mesenteric artery with the duodenum, showed the same neuron density as the duodenojejunal flexure. In this paper the 2 parts with higher neuron density were related to functional sphincteric zones, previously described.     

The role of secretin in the control of gastric secretion and emptying in the dog

It is well established that duodenal acidification strongly inhibits gastric acid secretion, gastric emptying rate and gastrin release. These effects are at least partly mediated via hormonal pathways, but it is not known whether they are mediated by the release of one peptide named in the past enterogastrone, or by several peptides acting together. The effects of duodenal acidification on gastric acid secretion and gastrin release can be reproduced by infusion of small doses of secretin and plasma secretin levels increase during duodenal acidification or after a meal. This peptide is thus the most probable candidate as an enterogastrone. It has however never been clearly shown that administration of low doses of secretin do decrease gastric emptying rate as well as acid secretion. Experiments were performed on four dogs with gastric fistulas. A peptone solution was infused into the stomach. The experiments were repeated during infusion of synthetic secretin. Our results indicate that infusion of low doses of secretin reproduce all the effects of duodenal acidification: a significant inhibition of gastric acid secretion, gastrin release and gastric emptying rate.     

Duodenum electrical stimulation delays gastric emptying, reduces food intake and accelerates small bowel transit in pigs

Duodenum electrical stimulation (DES) has been shown to delay gastric emptying and reduce food intake in dogs. The aim of this study was to investigate the effects of DES on gastric emptying, small bowel transit and food intake in pigs, a large animal model of obesity. The study consisted of three experiments (gastric emptying, small bowel transit, and food intake) in pigs implanted with internal duodenal electrodes for DES and one or two duodenal cannulas for gastric emptying and small bowel transit. We found that (i) gastric emptying was dose-dependently delayed by DES of different stimulation parameters; (ii) small bowel transit was significantly accelerated with continuous DES in proximal intestine but not with intermittent DES; (iii) DES significantly reduced body weight gain with 100% duty cycle (DC), but not with DES with 40% DC. A marginal difference was noted in food intake among 100% DC session, 40% DC session, and control session. DES with long pulses energy-dependently inhibits gastric emptying in pigs. DES with appropriate parameters accelerates proximal small bowel transit in pigs. DES reduces body weight gain in obese pigs, and this therapeutic effect on obesity is mediated by inhibiting gastric emptying and food intake, and may also possibly by accelerating intestinal transit. DES may have a potential application to treat patients with obesity.     

Emptying of the abomasum in adult ruminants

In the adult ruminant, abomasal emptying is a permanent phenomenon depending upon meal volume. Intradian rhythm involving the motor pattern of the duodenum and circadian rhythm of unknown origin modulate the transpyloric flow rate. The fundic tone, antro-duodenal coordination and pyloric resistance regulate gastric outflow. The break-like function of the pyloric resistance involves chyme viscosity. Transpyloric flow rate is controlled by a hierarchy of extrinsic and intrinsic mechanisms triggered at the duodenal level. The vagus permanently inhibits the motility of the abomasum. A similar relationship is observed between the pyloric sphincter and duodenal motility. Removal of the pyloric ring leads to an increased food intake.     

Gastric control of duodenal electric activity--the function of the gastroduodenal junction.

An investigation was made into the links between electric activity of antral and of duodeno-jejunal musculature in different functional conditions. The function of the gastroduodenal junction in this linking mechanism was analysed. The following observations were made: (a) in the absence of gastric stimulation, the slow electric activities of stomach and duodenum appear to be completely independent; (b) the gastroduodenal junction evidences no electric activity of its own but is affected by that of the two adjacent structures; (c) chemical stimulation of the gastric mucosa causes activation of the electric and mechanical activity of the stomach and analogous activation of duodenal musculature; this effect is mediated by the gastroduodenal junction; (d) very probably, the transmission of gastric activation to the duodenum is myogenic for it ceases after surgical transection but not after cooling or after ligature. The possible functional role of the pyloric junction in the complex gastroduodenal mechanism is discussed.     

Regulation of gastric emptying

Studies carried out in the years since William Beaumont's direct observations of gastric motility have provided increased understanding of the physiological roles of the stomach and of the mechanisms for the regulation of gastric motility. Tonic contractions of the proximal stomach are of primary importance for transfer of liquids from the stomach to the duodenum. Peristaltic contractions of the distal stomach are of primary importance for reducing the size of solid food particles and for transfer of solids to the duodenum. Because gastric emptying requires a net antral-duodenal pressure gradient, contractions of the duodenum also influence the rate of gastric emptying. Gastrointestinal hormones, including gastrin, cholecystokinin, secretin, somatostatin, and others, are released by contact of chyme with the intestinal mucosa, and affect contractions of the proximal stomach, distal stomach, and duodenum. Neural reflexes that arise from the stomach act through autonomic motor nerves to allow regulation by the central nervous system of gastric motility. gamma-Aminobutyric acid, opioids, and bombesin may serve as central neurochemical regulators of gastric motility.     

Transcytosis of gastric leptin through the rat duodenal mucosa

Leptin is secreted into the gastric juice by epithelial Chief cells and reaches the duodenum in a biologically intact active form. We assessed the possibility that this gastric leptin crosses the intestinal mucosa by transcytosis through enterocytes to reach blood circulation. Endogenous gastric leptin secretion was triggered by cholinergic stimulation. In another set of experiments, recombinant leptin was inserted in vivo into the duodenal lumen. Plasma levels of leptin were assessed by enzyme immunoassay and Western blot, and duodenal tissue was processed for immunocytochemistry. We first observed that leptin was found inside duodenal enterocytes from fed rats but not inside those from fasted ones. Stimulation of gastric secretion by a cholinergic agent led to rapid increases in plasma leptin levels (202 +/- 39%) except when the pylorus was clamped. Insertion of recombinant leptin into the duodenal lumen raised plasma leptin concentrations (558 +/- 34%) quite rapidly, whereas carrier solution without leptin had no effect. The use of FITC-tagged leptin reinforced these results. Light and electron microscopy revealed the cellular compartments involved in its transcytosis, namely, the enterocyte microvilli, the endocytotic vesicles, the Golgi complex, and the basolateral interdigitations. Leptin was also present in the lamina propria, in capillary endothelial cell plasmalemmal vesicles, and in capillary lumina. These results demonstrate that gastric exocrine leptin is internalized by duodenal enterocytes and delivered to the lamina propria and blood circulation. It may thus be able to play important paracrine and endocrine functions for the control of gastric emptying and nutrient absorption.     

Role of vagus nerve in postprandial antropyloric coordination in conscious dogs

It is generally believed that gastric emptying of solids is regulated by a coordinated motor pattern between the antrum and pylorus. We studied the role of the vagus nerve in mediating postprandial coordination between the antrum and pylorus. Force transducers were implanted on the serosal surface of the body, antrum, pylorus, and duodenum in seven dogs. Dogs were given either a solid or a liquid meal, and gastroduodenal motility was recorded over 10 h. Gastric emptying was evaluated with radiopaque markers mixed with a solid meal. Dogs were treated with hexamethonium, N(G)-nitro-l-arginine methyl ester (l-NAME), or transient vagal nerve blockade by cooling. A postprandial motility pattern showed three distinct phases: early, intermediate, and late. In the late phase, profound pyloric relaxations predominantly synchronized with giant antral contractions that were defined as postprandial antropyloric coordination. A gastric emptying study revealed that the time at which gastric contents entered into the duodenum occurred concomitantly with antropyloric coordination. Treatment by vagal blockade or hexamethonium significantly reduced postprandial antral contractions and pyloric relaxations of the late phase. l-NAME changed pyloric motor patterns from relaxation dominant to contraction dominant. Solid gastric emptying was significantly attenuated by treatment with hexamethonium, l-NAME, and vagal blockade. Postprandial antropyloric coordination was not seen after feeding a liquid meal. It is concluded that postprandial antropyloric coordination plays an important role to regulate gastric emptying of a solid food. Postprandial antropyloric coordination is regulated by the vagus nerve and nitrergic neurons in conscious dogs.     

Role of cholecystokinin in postprandial and vagally stimulated duodenal and gallbladder motility in dogs.

This study was designed to determine the role of cholecystokinin (CCK) in postprandial motility pattern of the duodenum and gallbladder (GB) in conscious dogs provided with chronic duodenal electrodes for recording of myoelectric activity and GB fistulas for measurement of intraluminal pressure and volume of GB and to calculate the GB motility index (MI) and GB emptying rate. During naturally occurring activity front (phase III MMC) in the duodenum there was significant increase in the MI of GB accompanied by about 20-30% reduction in the GB volume. These changes in duodenal and GB motility pattern could be duplicated by i.v. motilin. Feeding abolished the appearance of spontaneous activity front in the duodenum and greatly increased motility of GB while reducing its volume. Administration of CCK receptor antagonists in fed dogs failed to affect the motility changes induced by meal in the duodenum but abolished these of the GB. Vagal cholinergic stimulation with insulin, 2DG or urecholine caused similar effects to that induced by food i.e. increased duodenal spike activity, abolished phase III of the MMC, decreased GB volume and increased GB motility. Pretreatment with CCK antagonists did not affect significantly duodenal spike activity or GB motility but significantly increased the GB volume. Atropine 125 micrograms/kg) blocked almost completely spontaneous activity front in the duodenum and accompanying alterations in the motility and volume of GB. We conclude that CCK contributes to the MMC related alterations in the GB motor activity and is essential in cholinergic stimulation induced of the GB emptying but not in vagally induced duodenal and GB motility.     

By-passing the sphincter of Oddi does not affect gallbladder emptying in the pig

A study of the relationship between bile secretion and nutrition in the pig requires a complete and continuous collection of the bile and its reinfusion to the animal. In most of the studies performed in different species, bile has been directly reinfused into the duodenum, leading to the exclusion of the sphincter of Oddi from the biliary pathway. It has been postulated that such an exclusion could inhibit gallbladder emptying. The aim of the present work was to study postprandial gallbladder emptying in the pig, depending on the site of bile reinfusion, i.e. the duodenum or the lower bile duct. The gallbladder bile was coloured with indocyanine green (ICG) and marker secretion was recorded after a test-meal. The results showed that after meal intake, the gallbladder emptied over a similar period of time and according to similar kinetics, whatever the site of bile reinfusion.     

The role of gastric and duodenal pH in the cysteamine-induced duodenal ulcer in the rat

Many secretory studies reported an increase in gastric acid secretion by the duodenal ulcerogen cysteamine. A detailed analysis of these experiments, especially the results from rats with chronic gastric fistula suggest that direct stimulation of gastric acid secretion may not be the primary mechanism of the duodenal ulcerogenic action of cysteamine. We used a different approach and measured the pH at the site of ulceration in the proximal duodenum. A duodenal ulcerogenic dose of cysteamine did not change the pH at the anterior or posterior wall of the duodenum during 4 hr. In the same dose and by the same route of administration, cysteamine nevertheless induced duodenal ulcers in 24 hr. These experiments demonstrate that in addition to the effect on gastric acid secretion, other factors are needed to the effect on gastric acid secretion, other factors are needed to explain the early duodenal ulcerogenic action of cysteamine.     

Obestatin对血浆ghrelin和nesfatin-1水平及胃排空的影响

目的:探讨侧脑室注射obestatin对大鼠血浆酰基化ghrelin、去酰基化ghrelin、nesfatin-1水平的影响以及对胃排空的调控。方法:侧脑室注射obestatin,采用酶免疫测定(EIA)法检测血浆酰基化ghrelin、去酰基化ghrelin、nesfatin-1水平以及胃排空率的变化。结果:侧脑室分别注射0.1、0.3或1.0 nmol obestatin,大鼠血浆酰基化ghrelin、去酰基化ghrelin以及nesfatin-1水平无显著改变(P0.05),且酰基化ghrelin与去酰基化ghrelin比率无显著改变(P0.05);侧脑室注射obestatin,大鼠摄食量无显著改变,但胃排空率明显增加(P0.05);胃排空率明显延迟(P0.05)。与侧脑室注射1.0 nmol Obestatin组相比,注射1.0 nmol Obestatin+CRF,大鼠摄食量无显著改变,胃排空率明显延迟(P0.05)。各组摄食量及进入十二指肠内食物量无明显差异(P0.05)。结论:中枢obestatin促进大鼠的胃排空,可能与h/r CRF通路有关。     

Influences of food particle size and dietary energy content on patterns of gastric evacuation in fish: test of a physiological model of gastric emptying

The evacuation of food from the stomach is probably not a continuous smooth process but may occur in a pulse-like (step-wise) fashion. It is hypothesised that the pattern of emptying is influenced by feedback signals from receptors located in the upper intestinal tract and by factors affecting the rate of physical/chemical breakdown of the food particles. Mathematical functions used for describing evacuation patterns imply that emptying is continuous and they are, therefore, at best, only approximations. It was predicted that different mathematical expressions would give best fit to empirical data from gastric evacuation studies dependent upon the experimental conditions employed. An analysis of published data supported the predictions and revealed that an exponential function best described the evacuation of small, easily digested prey items, but a linear expression gave the best fit to data of the emptying of large food items. It is suggested that differences in surface-to-volume ratios between large and small food particles and the friabilities of different food types are important in determining the pattern of emptying. Whilst dietary energy content also appears to be an important factor in the governing of gastric evacuation, it appears that emptying pattern in fish species is rather less sensitive to changes in dietary composition than is gastric emptying in mammals.     

Lack of pyloric interstitial cells of Cajal explains distinct peristaltic motor patterns in stomach and small intestine

The frequency and propagation velocity of distension-induced peristaltic contractions in the antrum and duodenum are distinctly different and depend on activation of intrinsic excitatory motoneurons as well as pacemaker cells, the interstitial cells of Cajal associated with Auerbach's plexus (ICC-AP). Because ICC are critical for coordination of motor activities along the long axis of many regions in the gut, the role of ICC in antroduodenal coordination was investigated. We used immunohistochemistry, electron microscopy, simultaneous multiple electrical recordings in vitro, and videofluoroscopy in vivo in mice and rats. A strongly reduced number of ICC-AP with loss of network characteristics was observed in a 4-mm area in the rat and a 1-mm area in the mouse pyloric region. The pyloric region showed a slow wave-free gap of 4.1 mm in rats and 1.3 mm in mice. Between antrum and duodenum, there was no interaction of electrical activities and in the absence of gastric emptying, there was no coordination of motor activities. When the pyloric sphincter opened, 2.4 s before the front of the antral wave reached the pylorus, the duodenum distended after receiving gastric content and aboral duodenal peristalsis was initiated, often disrupting other motor patterns. The absence of ICC-AP and slow wave activity in the pyloric region allows the antrum and duodenum to have distinct uncoordinated motor activities. Coordination of aborally propagating peristaltic antral and duodenal activity is initiated by opening of the pylorus, which is followed by distention-induced duodenal peristalsis. Throughout this coordinated motor activity, the pacemaker systems in antrum and duodenum remain independent.