A stomach road or "Magenstrasse" for gastric emptying

Gastric muscle contractions grind and mix solid/liquid meal within the stomach, and move it into the bowels at a controlled rate. Contractions are of two types: slow volume-reducing contractions of the proximal stomach (the fundus), and peristaltic contraction waves in the distal stomach (the antrum). Fundic squeeze maintains gastro-duodenal pressure difference to drive gastric emptying. Emptying is generally assumed to proceed from the antrum to the fundus, so that ingested drugs can take hours to enter the small intestines and activate. Antral contraction waves (ACW), in contrast, generate fluid motions that break down and mix gastric content. Using a computer model of the human stomach, we discover a new function of these contraction waves apart from grinding and mixing. In coordination with fundic contraction, antral contraction waves move liquid content from the fundus along a very narrow path to the duodenum through the center of the antrum. Using physiological data, we show that this gastric emptying "Magenstrasse" (stomach road) can funnel liquid gastric content from the farthest reaches of the fundus directly to the intestines within 10 min. Consequently, whereas drugs (tablets, capsules, liquid) released off the Magenstrasse may require hours to enter the duodenum, at low concentration, when released on the Magenstrasse the drug can enter the duodenum and activate within 10 min-at high concentration. This discovery might explain observed high variability in drug initiation time, and may have important implications to both drug delivery and digestion, as well as to other wall-driven emptying of elastic containers.     

Gastric and duodenal motility in the cat: the role of central innervation assessed by transient vagal blockade

Experiments were performed on four cats to characterize fasting gastric and small bowel motility and to assess the role of extrinsic vagal innervation in the control of that motor activity. A multilumen manometry tube was positioned to record pressure changes from the proximal small bowel and stomach. Transient vagal nerve blockade was accomplished by cooling the cervical vagosympathetic nerve trunks, previously isolated in skin loops on each side of the neck. Two characteristic patterns of basal activity were documented in the stomach: (i) regular phasic contractions of variable amplitude in the body of the stomach; and (ii) infrequent, irregular contractions of high amplitude in the distal antrum. In the duodenum, two predominant activity patterns were noted: (i) periods of continuous irregular activity; and (ii) irregular clusters of contractions separated by quiescent intervals. No typical migrating motor complex activity was seen in the basal gastric or small bowel recordings. Bilateral vagal blockade did not consistently change the general pattern of gastric or small bowel activity, but did appear to reduce gastric contractile activity, as measured by motility indices. We conclude that extrinsic vagal innervation does not play a major role in the control of fasting feline gastric and duodenal motility.     

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.     

Sexual differences of the inhibitory effect of ethanol on gastrointestinal motility: in vivo and in vitro studies

Female brain is more sensitive to the acute exposure of ethanol. This study aimed to investigate the sexual difference of the ethanol-induced inhibition of gastrointestinal motility. Wistar rats were fasted and allowed drinking water only 12 - 18 h before the experiments. In the in vivo experiments, by using an oral radiochromium motility marker, the liquid gastric emptying and intestinal transit were [corrected] measured 30 min after ethanol treatment. In the in vitro study, strips of stomach and duodenum smooth muscle were suspended in organ baths containing Krebs solution, and their isometric contractions were also examined. Systemic administration of ethanol (2 g/kg, i.p.) significantly inhibited the gastric emptying and intestinal transit, and the effect on female rats turned out to be greater than that on the male rats (P < 0.05). In an in vitro study, ethanol (0.38 x 10(-3) M - 1.34 x 10(-3) M) inhibited the motility of gastric antrum and duodenum in rats of both sexes, but there was no sexual difference in the inhibitory effect of ethanol on muscle strips. We concluded that sexual difference of the ethanol-induced inhibition of gastrointestinal motility was not resulted from the smooth muscle itself.     

Gastric flow and mixing studied using computer simulation

The fed human stomach displays regular peristaltic contraction waves that originate in the proximal antrum and propagate to the pylorus. High-resolution concurrent manometry and magnetic resonance imaging (MRI) studies of the stomach suggest a primary function of antral contraction wave (ACW) activity unrelated to gastric emptying. Detailed evaluation is difficult, however, in vivo. Here we analyse the role of ACW activity on intragastric fluid motions, pressure, and mixing with computer simulation. A two-dimensional computer model of the stomach was developed with the 'lattice-Boltzmann' numerical method from the laws of physics, and stomach geometry modelled from MRI. Time changes in gastric volume were specified to match global physiological rates of nutrient liquid emptying. The simulations predicted two basic fluid motions: retrograde 'jets' through ACWs, and circulatory flow between ACWs, both of which contribute to mixing. A well-defined 'zone of mixing', confined to the antrum, was created by the ACWs, with mixing motions enhanced by multiple and narrower ACWs. The simulations also predicted contraction-induced peristaltic pressure waves in the distal antrum consistent with manometric measurements, but with a much lower pressure amplitude than manometric data, indicating that manometric pressure amplitudes reflect direct contact of the catheter with the gastric wall. We conclude that the ACWs are central to gastric mixing, and may also play an indirect role in gastric emptying through local alterations in common cavity pressure.     

Gastric Electrical‐Stimulation Effects on Canine Gastric Emptying,Food Intake,and Body Weight

Objective: It has been reported that electrical stimulation at the distal stomach can disrupt intrinsic gastric electrical activity and delay gastric emptying. Gastric dysrhythmia and impaired gastric emptying are associated with upper gastrointestinal symptoms and weight loss. The purpose of this study was to evaluate the effect of low‐frequency/long‐pulse gastric electrical stimulation (GES), at proximal and distal stomach, on canine gastric emptying, food intake, and body weight. Research Methods and Procedures: Eight dogs were surgically implanted with four pairs of electrodes along the greater curvature and a gastric tube at the dependent part of the stomach. Liquid gastric emptying at baseline, during proximal and distal GES at 6 cycles per minute, was assessed first by a dye dilution technique. Proximal and distal GES were then randomly delivered during feeding for 10 consecutive days, and food intake and body weight were recorded daily. Results: There was no significant difference in gastric emptying parameters among the various sessions. The mean daily food consumption was significantly reduced during both sessions of GES, resulting in significant immediate weight loss. Percentage weight loss was comparable between both sessions of GES. Discussion: Short‐term GES significantly reduced canine food intake and weight. This effect may not be related to changes in gastric emptying. GES may have a potential role in the treatment of obesity.     

PYY immunoneutralization does not alter lipid-induced inhibition of gastric emptying in rats

PYY is released from the distal ileum by fat and may be involved in mediating lipid-induced inhibition of gastric acid secretion and intestinal motility. The role of PYY in intestinal lipid-induced inhibition of gastric emptying in awake rats was investigated using a specific polyclonal antibody raised against PYY. METHODS: Gastric emptying of liquids was measured in awake rats fitted with a Thomas gastric cannula. Intralipid (total dose 50 or 100 mg) was perfused for 10 min (0.05 ml/min) into a duodenal (n = 11) or mid-intestinal cannula (60 cm from Ligament of Treitz; n = 8), and gastric emptying was measured over the 5-10 min period. Gastric emptying was measured 15 min after IP injection of PYY (1 nmol/rat). PYY antibody (20 mg) or a control antibody (anti-KLH; keyhole limpet hemocyanin) was injected ip 8-12 h before experiments. RESULTS: Exogenous PYY (1 nmol) inhibited gastric emptying and administration of PYY antibody blocked this response. Perfusion of lipid (50 and 100 mg) into the proximal intestine produced a 46% and 66% inhibition of gastric emptying respectively. Inhibition of gastric emptying in response to 50 mg lipid in the proximal small intestine was unaffected by administration of PYY antibody but was abolished by administration of the CCK A receptor antagonist devazepide (0.1 mg/kg ip). Perfusion of lipid into the distal intestine (50 and 100 mg) inhibited gastric emptying by 10% and 32% respectively. Inhibition of gastric emptying in response to 100 mg lipid in the distal intestine was unaffected by PYY antibody. CONCLUSIONS: Lipid perfused into either the proximal or distal intestine inhibits gastric emptying via a PYY-independent mechanism. CCK is involved in proximal lipid induced inhibition of gastric emptying.     

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.     

Suppression of vagal motor activities evokes laryngeal afferent-mediated inhibition of gastric motility

We previously reported that the activation of water-responsive afferents in the superior laryngeal nerve was responsible for the inhibition of gastric motility. The present study was undertaken to clarify the roles of the vagal preganglionic neurons responsible for laryngeal afferent-mediated inhibition of gastric motility. Intravenous injection of atropine abolished the inhibition of motility in both the distal and the proximal stomach induced by water administration into the larynx. The neurons in the dorsal motor nucleus of the vagus (DMV), which project to the abdominal viscera, were exclusively inhibited by water administration. Taken together, inhibition of neurons in the DMV induces inhibition of gastric motility evoked by laryngeal water-responsive afferents via a cholinergic pathway. Because chemical lesions of the intermediate DMV, but not the caudal DMV, abolished the inhibition of the distal stomach motility induced by water administration, the intermediate DMV is responsible for the inhibition shown in the distal stomach.     

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.     

Glucose acts in the CNS to regulate gastric motility during hypoglycemia

Our purposes were to 1) develop an animal model where intravenously (iv) administered d-glucose consistently inhibited antral motility, and 2) use this model to assess whether iv glucose acts to inhibit motility from a peripheral or a central nervous system site and to elucidate the factor(s) that determine(s) whether stomach motor function is sensitive to changes in blood glucose. Rats were anesthetized with alpha-chloralose-urethane, and antral motility was measured by a strain-gauge force transducer sutured to the antrum. In some cases, antral motility and gastric tone were measured by monitoring intragastric balloon pressure. Increases in blood glucose were produced by continuous iv infusion of 25% d-glucose at 2 ml/h. Inhibition of antral motility and gastric tone was observed when gastric contractions were induced by hypoglycemia (subcutaneously administered insulin, 2.5 IU/animal). In contrast, no inhibition of gastric motor function was observed when glucose infusion was tested on gastric contractions that were 1) spontaneously occurring, 2) evoked by iv administered bethanechol in vagotomized animals, and 3) evoked by the TRH analog RX77368, microinjected into the dorsal motor nucleus of the vagus. Using the model of insulin-induced hypoglycemia to increase gastric motor activity, we found that neither sectioning the hepatic branch of the vagus (n = 5), nor treating animals with capsaicin to destroy sensory vagal afferent nerves (n = 5) affected the ability of iv d-glucose to inhibit gastric motor function. Our results indicate that an important factor determining whether stomach motor function will be sensitive to changes in blood glucose is the method used to stimulate gastric contractions, and that the primary site of the inhibitory action of iv glucose on gastric motility is the central nervous system rather than the periphery.     

Chronic tachygastrial electrical stimulation reduces food intake in dogs

Objective: Tachygastria is known to be associated with gastric hypomotility. This study investigated the effect of tachygastrial electrical stimulation (TES) on food intake and its effects on gastric motility. Research Methods and Procedures: Five experiments were performed to study the effects of TES on gastric slow waves, gastric tone, accommodation, and antral contractions, gastric emptying, acute food intake, and chronic food intake in dogs. Results: TES at tachygastrial frequencies induced tachygastria and reduced normal slow waves. TES significantly reduced gastric tone or induced gastric distention, impaired gastric accommodation, and inhibited antral contractions. TES significantly delayed gastric emptying. Acute TES reduced food intake but did not induce any noticeable symptoms. Chronic TES resulted in a 20% reduction in food intake, and the effect of TES was found to be related to specific parameters. Discussion: TES at the distal antrum results in a significant reduction in food intake in dogs, and this inhibitory effect is probably attributed to TES‐induced reduction in proximal gastric tone, gastric accommodation, antral contractility, and gastric emptying. These data suggest a therapeutic potential of the specific method of TES for obesity.     

Effect of protein, fat, carbohydrate and fibre on gastrointestinal peptide release in humans

Short-term regulation of food intake controls what, when and how much we eat within a single day or a meal. This regulation results from an integrated response to neural and humoral signals that originate from the brain, gastrointestinal (GI) tract and adipose tissue. In the GI tract, multiple sites including the stomach, duodenum, distal small intestine, colon, and pancreas are involved in this process. Ingested food evokes satiety by mechanical stimulation and by release of peptides in the GI tract. The intestine in particular plays a key role in satiety through various peptides secreted in response to food. Many of the intestinal peptides inhibit also gastric emptying thus enhancing gastric mechanoreceptor stimulation. In this review, the current knowledge about the effects of different macronutrients and fibre on the release of GI satiety-related peptides in humans is discussed.     

Spawning period and migration of three species of cyprinids in a stream with Mediterranean regimen (SW Spain)

These studies investigated the effects of somatostatin on gastric motility in the rainbow trout. Two experimental models were used, the isolated vascularly-perfused stomach and isolated strips of gastrointestinal smooth muscle. Both models demonstrated that somatostatin can inhibit gastrointestinal motility and may therefore modulate gastric emptying in fish.
In the vascularly-perfused stomach, somatostatin (10–1000 n m ) decreased maximum and baseline intragastric pressure by 10–20% in the presence of stimulatory doses of carbachol or 5-hydroxytryptamine. In addition, somatostatin (1 μ m ) inhibited by 50% the magnitude of spontaneous contractions generated by distension. Somatostatin had little effect on the pressure gradient or contractile frequency. These results suggest that somatostatin may negatively modulate gastric emptying in the rainbow trout.
In isolated gastric smooth muscle strips, somatostatin (100 pmol) inhibited tension stimulated by carbachol (circular orientation of muscle) or 5-hydroxytryptamine (longitudinal orientation). These results correlated with those observed in the vascularly perfused stomach preparation. Somatostatin also decreased tension stimulated by carbachol and 5-hydroxytryptamine in intestinal smooth muscle strips, suggesting that under some conditions somatostatin could increase gastric emptying rate by relaxing intestinal musculature.     

Region-specific effects of STW 5 (Iberogast®) and its components in gastric fundus,corpus and antrum

Functional dyspepsia (FD) is a disorder that involves impaired gastric accommodation, antral hypomotility, and upper abdominal pain. The herbal drug STW 5 (Iberogast^®) is used to successfully treat FD patients. Here, we report in vitro data revealing the mode of action of STW 5 and its individual herbal extracts on gastric motility. STW 5 evoked a relaxation of the proximal stomach but increased antral motility. Both effects are myogenic. The extracts of Angelica root, chamomile flower and liquorice root mimicked the inhibitory effects in the proximal stomach whereas the extracts of greater celandine herb, Melissa leaf, caraway fruit and bitter candy tuft increased motility of the proximal stomach. All extracts increased motility in the antrum comparable to the effects of STW 5. We conclude that the differential effects of STW 5 on proximal and distal stomach motor activity are not caused by solely spasmolytic or anti-spasmolytic effects of the individual components. It is suggested that the individual extracts target transduction mechanisms that are specifically expressed in the proximal vs. distal stomach. We present a rationale for the differential effect of STW 5 which is a result of the combined actions of its individual components and reason that the inhibitory effects in the proximal and the excitatory effects in the distal stomach may contribute to symptom relief in FD patients treated with STW 5 (Iberogast^®).     

Effects of neurotensin on motor patterns of canine duodenum and proximal jejunum

The aim of this study was to clarify if small doses of neurotensin (2.5 and 5.0 pmol.kg-1.min-1, i.v.) in dogs alter the postprandial motor pattern of the duodenum in comparison with the adjacent jejunum. The intestinal motor patterns were quantified by means of closely spaced strain gauge transducers and a computerized method. An acaloric viscous meal of cellulose was used to induce postprandial motility. Gastric emptying was measured radiographically. During intravenous control infusion of saline, the characteristics of duodenal and jejunal motor pattern were significantly different. The duodenum contracted at a lower rate and showed a higher incidence of stationary contractions. The lower dose (2.5 pmol.kg-1.min-1) of neurotensin showed no significant effects, whereas the higher dose (5 pmol.kg-1.min-1) significantly slowed gastric emptying and altered the motor pattern of both intestinal segments in a similar manner. It reduced the number of contractions, shortened the contraction spread, increased the incidence of stationary contractions, and decreased the incidence of propagated contractions. The alterations of motility caused enhanced mixing of luminal contents. The differences in motor patterns seen in the control state between both intestinal segments were diminished during neurotensin. Data revealed no differences in sensitivity of the duodenum and jejunum to neurotensin. Results suggest that neurotensin is one of the gastrointestinal peptides involved in regulating intestinal contractile patterns.     

Hormonal component of the postprandial motility response of the proximal stomach in dogs

The motility of a proximal gastric pouch, that has been extinsically denervated by autotransplantation, has been studied in 4 dogs. In the same time, the electrical activity of the duodenum was recorded with AgAgCl electrodes. Recordings were made in the fasting state and after oral administration of 250 ml NaCl 154 mM solutions containing 15 kcal/kg of either glucose, peptides or lipids, or 3 X 5 kcal/kg of a mixture of these three nutrients. The results showed, in the fasting state, that a cyclic activity took place in the denervated gastric pouch corresponding to the myoelectric complex observed at the same time in the duodenum. After feeding the dogs with any nutrient solution, we observed: 1) a decrease in pouch pressure; 2) an interruption of the cyclic activity in both the pouch and duodenum. A fasting motility resumed simultaneously in both the pouch and duodenum. These results indicate that hormonal agents are involved in the motility of the proximal stomach as well as in the postprandial interruption of the myoelectric complex.     

Opioid-induction of migrating motor activity in chickens.

Enkephalin and morphine initiation of phase III of MMC has been reported in dog and humans. In chickens, a similar migrating activity initiated at the duodenum occurs 7-9 times a day while the gastric activity ceases. The main objective was to determine whether this migrating activity could be induced by opioids. Electrodes for electromyography were implanted in the stomach, proximal and distal duodenum, jejunum and proximal and distal ileum of 4 wk old chickens. Met-enkephalin, morphine and beta-casomorphin-5 (5 x 10(-7) moles/Kg) were infused i.v.. All these substances initiated an intestinal migrating activity concurrent with gastric inhibition. The mean duration of gastric inhibition depended on the substance, lasting from 5 min (met-enkephalin) to 27 min (beta-casomorphin-5). The migrating activity started in the distal duodenum and propagated to the ileum in about 18 min. These effects were partially blocked by naloxone at equimolar doses. In conclusion, in chickens, as in dogs and humans, migrating myoelectrical activity can be initiated by opioids.     

The control of gut motility

Gut motility in non-mammalian vertebrates as in mammals is controlled by the presence of food, by autonomic nerves and by hormones. Feeding and the presence of food initiates contractions of the stomach wall and subsequently gastric emptying, peristalsis, migrating motor complexes and other patterns of motility follow. This overview will give examples of similarities and differences in control systems between species. Gastric receptive relaxation occurs in fish and is an enteric reflex. Cholecystokinin reduces the rate of gastric emptying in fish as in mammals. Inhibitory control of peristalsis is exerted, e.g. by VIP, PACAP, NO in fish and amphibians, while excitatory stimuli arise from nerves releasing tachykinins, acetylcholine or serotonin (5-HT). In crocodiles, we have found the presence of the same nerve types, although the effects on peristalsis have not been studied. Recent studies on signal transduction in the gut smooth muscle of fish and amphibians suggest that external Ca2+ is of great importance, but not the only source of Ca2+ recruitment in tachykinin-, acetylcholine- or serotonin-induced contractions of rainbow trout and Xenopus gastrointestinal smooth muscle. The effect of acetylcholine involves reduction of cAMP-levels in the smooth muscle cells. It is concluded that, in general, the control systems in non-mammalian vertebrates are amazingly similar between species and animal groups and in comparison with mammals.     

Feedback regulation of pancreatic secretion by peptide YY

The present status of our understanding of the feedback regulation of pancreatic secretion by peptide YY (PYY) released from the distal intestine is reviewed. Exocrine pancreatic secretion is primarily controlled by the cephalic (the vagus nerve), gastric (acid and pepsin secretion, and nutrients delivered into the duodenum by gastric emptying), and intestinal (secretin and CCK) mechanisms. PYY acts on the multiple sites in the brain and gut, and inhibits pancreatic secretion by regulating these primary control mechanisms. The involvement of Y(1) and Y(2) receptors has been suggested in the regulation of pancreatic secretion. However, it remains to be studied which site of action or receptor subtype is physiologically most important for this regulation.