Gastroduodenal Junction Research Articles

Antroduodenal coordinated contractions as studied by chemical ablation of myenteric neurons in the gastroduodenal junctional zone.

Antroduodenal contractions were studied in rat preparations. Augmented duodenal contractions occurred spontaneously in coordination with antral contractions in normal and saline-pretreated preparations. The coordination did not occur when muscle layers and the myenteric plexus were transversely cut at the duodenum just anal to the gastroduodenal junction. In silent preparations, the coordinated contractions were produced by neostigmine or domperidone. When the antroduodenal junctional zone was pretreated with benzalkonium chloride, the augmented duodenal contractions did not occur spontaneously, and even after administration of neostigmine and domperidone although antral contractions occurred spontaneously. In these preparations, there were notably few myenteric neurons in the junctional zone, but the neurons were distributed normally in the areas where motility was recorded. The results suggest that myenteric neurons mediate antroduodenal coordinated contractions and that the coordination is modified by myenteric cholinergic excitatory and dopaminergic inhibitory pathways.

Diameter and Wall Thickness Recording of Canine Pylorus with Implantable Miniature Ultrasonic Transducers

Outer diameter and thickness of the muscular wall of canine pylorus were measured simultaneously by determining the distance between pairs of implanted ultrasonic transducers, evaluating the sonic transit time with a digital sonometer. For the study of the motility in the gastroduodenal transit zone, the ultrasonically determined pyloric responses were compared with signals from conventional strain-gauge transducers sutured to the neighboring duodenum and gastric antrum. After stimulation of the gastrointestinal motility by an intravenous bolus injection of cholecystokinin octapeptide, pyloric contractions with a frequency of 5.2 min-1 could be recorded for some minutes; those contractions were independent of the more rapid antral and duodenal motility. Together with the observed tonic constriction of the pyloric ring, which could be inhibited by intravenous injection of adrenaline, an autonomous role of the gastroduodenal junction as a true sphincter is supported.

Pyloric deformation from peptic disease

We have used double-contrast radiographic techniques to clarify what changes in the configuration and movements of the gastroduodenal junction result when peptic lesions involve the distal gastric segment between the proximal (PPL) and the distal pyloric muscle loop (DPL). Among 50 cases of pyloric ulceration diagnosed during a four-year study period, 18 cases fulfilled all study criteria. Ulcers maintained a consistent location with regard to the muscular structures of the pylorus, and by affecting these structures, led to many strange deformations of the gastric outlet including permanent pseudodiverticula and reversal of pyloric angulation. The most common site for peptic lesions in the pyloric segment was the protuberance of the lesser curvature called the pyloric torus; many torus lesions extended into and destroyed the DPL. This led to widening of the gastric outlet and radiographic evidence of increased duodenogastric reflux. Pyloric closure was further impaired in this setting because the mucosa no longer prolapsed into the gastric outlet and did not occlude the pyloric lumen as it normally does. Less common lesions involved the greater curvature and the PPL. In one patient, scarring of the PPL led to an antral web and gastric hyperperistalsis. This was the only patient who required operation for chronic gastric outlet obstruction. One-third of the 18 patients had reflux esophagitis in addition to peptic pyloric disease. In most patients without additional ulcerogenic risk factors, treatment with antisecretory agents led to the healing of ulcer craters. We conclude that the morphologic and functional changes of the gastric outlet caused by peptic lesions depend, in part, on the effect the ulcer has on the underlying pyloric musculature.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoradiographic and functional development of gastric cholecystokinin receptors in the rat

To determine the functional role for and the pharmacological specificity of developing gastrointestinal CCK receptors, in vitro pyloric contractility and autoradiographic CCK receptor binding were examined in pups aged 1–20 days. CCK contracted the gastroduodenal junction at all ages, while nonsulfated CCK-8 (d-CCK) was less potent. Autoradiographic studies revealed CCK binding localized to the gastroduodenal junction throughout development. MK-329, a specific type A CCK receptor antagonist, completely displaced 125I CCK-8 binding at all ages, while d-CCK displaced binding at ages at which d-CCK elicited gastroduodenal contractility. The results demonstrate a physiological role for and pharmacological specificity of neonatal gastroduodenal CCK receptors.

Excitatory and inhibitory neural regulation of canine pyloric smooth muscle

Studies were performed to characterize the intrinsic innervation of the circular muscle layer of the canine pylorus. Cross-sectional strips of muscle were studied with intracellular recording techniques, and junction potentials were elicited with transmural nerve stimulation. Neurally mediated responses were recorded from cells at several points through the thickness of the circular layer. Excitatory junction potentials (EJPs) increased and inhibitory junction potentials (IJPs) decreased in amplitude with distance from the myenteric border of the circular muscle. Atropine blocked EJPs throughout the circular layer, demonstrating that excitatory inputs are primarily cholinergic. The gradient in IJP amplitude persisted after blockade of EJPs. Three components of IJPs were identified: 1) a fast, apamin-sensitive component that reached a peak and decayed within approximately 1 s; 2) a slower, apamin-insensitive component that reached a peak within 800 ms but decayed slowly over 5 s; and 3) a very slow component that reached a maximum in 7-10 s. Junctional potentials affected the pattern of myogenic electrical activity. Transmural stimulation could evoke premature slow waves in the myenteric portion of the circular layer but when excitatory inputs were blocked, IJPs greatly reduced the amplitude of slow waves. EJPs elicited action potentials in submucosal portion of circular muscles, and IJPs hyperpolarized these cells. The influence of intrinsic nerves on contractile patterns of pyloric muscles was also characterized. These data demonstrate that a neuromuscular apparatus exists within the gastroduodenal junction for 1) local regulation of slow waves and 2) independent control of the myenteric and submucosal regions of the circular layer.

Selective vagal influences at the gastroduodenal junction in sheep

Selective vagal influences at the gastroduodenal junction in sheep

Organization of electrical activity in the canine pyloric canal.

1. The electrical activity of the canine gastroduodenal junction was investigated using cross-sectional muscle preparations and intracellular recording techniques. 2. Spontaneous electrical slow waves were recorded from antral and pyloric cells but not from duodenal cells adjacent to the pyloric region. Slow waves were generated in the antrum and propagated to the pyloric region via the circular layer. Pyloric slow waves consisted of an upstroke phase, a plateau phase and oscillations superimposed upon the plateau, whereas antral slow waves had smooth plateau potentials. 3. Within the pylorus slow waves decayed in amplitude with distance from the myenteric border of the circular muscle; the majority of pyloric circular cells were normally electrically quiescent. 4. The longitudinal muscle in the pylorus was electrically coupled and paced by the circular muscle. In longitudinal cells slow waves were usually of long duration with multiple spikes superimposed upon the plateau phase. 5. Nifedipine (10(-8) to 10(-5) M) decreased slow waves amplitude and duration. Tetraethylammonium ions (TEA; 10 mM) increased the duration of slow waves, caused spiking activity during the plateau phase and also elicited spiking in the quiescent regions. 6. The results suggest that gastric slow waves pace the myenteric portion of the circular muscle layer and the longitudinal layer of the pylorus, but do not traverse the gastroduodenal junction, nor pace the majority of cells within the circular muscle of the pylorus. Other excitatory mechanisms are necessary to activate these regions and to co-ordinate their motility with gastric motility.

Vagal Influences on the Phasic and Tonic Components of the Motility of the Ovine Stomach and Gastroduodenal Area

Both the phasic and tonic components of gastric motility including the gastroduodenal junction were recorded after section or cooling blockade of the vagus nerves in conscious sheep. The phasic contractile activity was monitored using electromyography, strain gauges, and intraluminal manometry. The changes in the tone of the stomach (abomasum) were assessed by an electronic barostat. The cyclical contractions of the reticulorumen ceased immediately after bilateral vagotomy, whereas the activity of the antral part of the abomasum was strongly enhanced. Two weeks after vagotomy, the abomasal hypermotility persisted while reticuloruminal movements developed from a local nervous network. Vagal cooling at 5°C of one of the vagus nerves after section of the contralateral vagus similarly inhibited reticuloruminal contractions in contrast to the occurrence of abomasal hypermotility. During vagal cooling, both the abomasal and pyloric tone were lowered. We conclude that vagal cooling impairs excitatory input to the reticulorumen and inhibitory input to the gastroduodenal junction. The decreased smooth muscle tone at the abomasal and pylorus levels during vagal cooling suggests that vagal stimulatory influences are abated.

Duodenal bulb control of the flow rate of digesta in the fasted and fed dog.

1. Continuous measurement of the flow of digesta near the pylorus, and 5 cm aborally, was assessed in the conscious dog using a chronically implanted flowmeter. The patterns of flow were related to motor activity of the gastroduodenal junction. 2. Electromagnetic measurement of the flow was calibrated in vitro by means of a pulsatile pump. Validation was obtained in vivo by direct evaluation of the amount of chyme collected from an open duodenal cannula and indirectly by a dye-dilution technique. 3. After a 12 h fast, only small amounts of gastric contents were delivered into the duodenum. This transfer occurred during periods of irregular motor activity recorded along the gastroduodenal junction, which occupied less than 25% of the recording time. The patterns of flow near the pylorus and beyond the duodenal bulb were correlated to antral and duodenal contractions respectively. 4. After a meal, gastric emptying occurred intermittently and was related to enhanced antral motor activity beyond the duodenal bulb; digesta flowed in clusters of gushes which were related to the duodenal contractions. 5. It is concluded that the mechanical role of the duodenal bulb is to change the intermittent juxtapyloric flow of digesta into a uniform flow at the duodenal level.

Pylorectomy reduces the satiety action of cholecystokinin.

Rat gastric cholecystokinin (CCK) receptors are localized to the circular muscle layer of the pyloric sphincter, and a role for these receptors in the mediation of CCK satiety has been proposed. To directly assess the contribution of this receptor population in CCK satiety, the area of the pyloric sphincter containing these receptors was surgically removed, and the behavioral responses to CCK were compared pre- and postpylorectomy. The presence of CCK receptors in the gastroduodenal junction was assessed by either in vitro CCK receptor autoradiography or in vitro contractile response to CCK. The results depended on the time after pylorectomy during which testing occurred. Two to 3 wk after pylorectomy rats demonstrated a significant attenuation of CCK satiety such that while the response to 1 and 2 micrograms/kg was intact, any additional inhibition by 4 and 8 micrograms/kg was eliminated. At this time, no evidence of CCK receptors around the gastroduodenal junction was found. In contrast, 2-3 mo after pylorectomy, the normal dose-response inhibition to CCK was intact. Evidence for the presence of CCK binding sites at the gastroduodenal junction was found by both autoradiography and physiological assessment. These results indicate a role for pyloric CCK receptors in the mediation of CCK satiety.

Radiation-induced changes in mouse duodenal papilla.

Radiation-induced changes in duodenal mucosal morphology as seen by scanning electron microscopy have been widely reported in the literature. However, no comment has previously been made on any post-irradiation alteration in the duodenal papilla. This paper describes the preliminary results of an investigation into the effects of X rays on the papilla. The duodenal papilla was difficult to find in untreated and sham irradiated mice. It was identified in only two of six mice examined and was located 5.37 and 4.43 mm from the gastroduodenal junction. Eighteen hours after irradiation with 15 Gy X rays, there was little change in position or prominence of the papilla. However, 3 days after treatment, the papilla was only 2.19-3.83 mm from the pylorus. It was also more prominent, being found in all three animals studied and having a widely dilated orifice in contrast to the closed structure seen in the unirradiated specimens. It is concluded that treatment with X rays alters the structure of the duodenal papilla. There may be implications for duodenal function in this marked change in the papilla, which controls the flow of pancreatic and biliary secretions.

Definition of gastroduodenal junction in healthy subjects.

To study the appearance and distribution of the normal mucosa at the gastroduodenal junction in man, 14 specimens of normal mucosa, eight obtained during pylorplasty, and "relatively" normal specimens from the distal stomach and whole duodenum were examined microscopically. Three histologically distinct types of normal duodenal mucosa were found at this junction. These were termed antral type duodenal mucosa, transitional type duodenal mucosa (which is also referred to as gastric surface epithelial metaplasia), and jejunal type duodenal mucosa. Antral type duodenal mucosa appeared as a series of finger-like processes 1-3 mm long, circumferentially located around the junction of the antrum and duodenum; transitional type duodenal mucosa extended 2-3 mm beyond this; and the rest of the mucosa was jejunal type duodenal mucosa. The mucosa of the pyloric antrum can therefore lie adjacent to antral type duodenal mucosa, or adjacent to either of the components of transitional type duodenal mucosa.

Gastric emptying of liquids in the fasted dog

Gastric emptying of different volumes of water was studied in the fasted dog. Volumes of water ranging from 25 ml to 500 ml at 20 ° C were administered during phase I of the fasted state by natural swallowing. Effluent was collected from a permanent Thomas cannula located in the duodenum about 15 cm from the gastroduodenal junction. The presence of phase I was ascertained by observing the discharge from the cannula prior to administration of water. Mucus and bile discharge was taken as phase II activity, and 20 min after cessation of any discharge motility was assumed to be phase I. Distinctly different patterns of fluid discharge were observed for volumes smaller than and larger than 100 ml. For small volumes a lag phase was observed before the discharge of stomach contents, with most of the discharge occurring at the onset of and during phase II. Large volume discharge on the other hand followed characteristic first-order kinetics, a finding consistent with many studies already reported in the literature. The results indicate that the stomach emptying pattern of water depends on the administered volume. While small volumes follow the existing motility pattern in the stomach, large volumes convert the stomach activity to a continuous ‘fed like’ state and result in a continuous discharge of liquid until most of the liquid is discharged and the fasted state is subsequently restored. The change of time required for discharge of half of the administered volume from 40 min to 10 min for small to large volumes suggests that this transition in the discharge patterns occurs between 100 and 150 ml for water in the fasted dog. Additional findings of this study are the pH changes associated with the different volumes of water. The pH of duodenal discharge was between 7 and 8 for small volumes and decreased progressively as the volumes were increased, being as low as 1.5 when 500 ml water was administered, indicating that large volumes apparently induce acid secretion in the stomach.

Novel autonomic neurotransmitters and upper gastrointestinal function

The evidence for, and possible roles of, inhibitory and excitatory non-adrenergic, non-cholinergic (NANC) nerves supplying smooth muscle, and the effects of putative transmitter candidates are considered for each of three main regions of the upper gastrointestinal tract: (A) the smooth muscle portion of the oesophagus and the oesophagogastric junction, (B) the stomach (fundus, body and antrum) and gastroduodenal junction and (C) the biliary tract and choledochoduodenal junction. The major points from human tissues are as follows: 1. Inhibitory (NANCI) nerves appear to be present in the muscularis externa of oesophagus, stomach and duodenum, with greater density in the circular than in the longitudinal muscle. 2. NANCI nerves are present in high density at the oesophagogastric and choledochoduodenal junctions. They may also be present at the gastroduodenal junction. The gall-bladder may have a very sparse NANCI innervation. 3. Excitatory (NANCE) nerves appear to be present throughout the upper gastrointestinal tract. 4. Many candidates need at present to be considered for the role of NANCE transmitter(s) in the human upper gastrointestinal tract but substance P still seems a likely contender for this role. 5. Fewer candidates are at present generally available for the role of NANCI transmitter(s), with VIP and ATP being leading contenders. However, in the human upper gastrointestinal tract the evidence for ATP is not good, and VIP still remains the favourite candidate except in the gall-bladder, where its role remains to be elucidated.

The vagal and spinal innervation of the gastro-duodenal junction of sheep.

This paper describes the distribution of vagal afferent, vagal preganglionic and thoraco-lumbar spinal afferent neurones to the gastro-duodenal junction of sheep which may form part of the structural basis for duodeno-gastric reflex mechanisms. After retrograde transport of cholera toxin-horseradish peroxidase (CT-HRP) from subserosal micro-injections into the gastro-duodenal junction, light-microscopic examination revealed CT-HRP-labelled cell bodies projecting from the medulla oblongata and the dorsal root ganglia. Medullary cell bodies were distributed bilaterally in the dorsal motor nucleus of the vagus (d.v.m.n.) 4.50 mm rostral and 2.52 mm caudal to a transverse plane through the obex. The sizes of brain-stem cell bodies, the extent of their dendritic arborization, axonal structure and orientation are described. Spinal sensory neurones were distributed to the thoraco-lumbar dorsal root ganglia T6-L3. Labelled cells and axons were found in the left and right vagal nodose ganglion. No labelled material was present in the lateral columns of the thoraco-lumbar spinal cord. A brain-stem map of medullary neurones was constructed from coronal sections of cresyl fast violet material. This enabled comparison between preparations and confirmed that all CT-HRP-labelled cell bodies and dendritic projections in the brain stem were confined to the d.v.m.n.

Development of cholecystokinin binding sites in rat upper gastrointestinal tract.

Autoradiography using 125I-labeled Bolton Hunter-CCK-33 was used to study the distribution of cholecystokinin binding sites at different stages of development in the rat upper gastrointestinal tract. Cholecystokinin (CCK) binding was present in the distal stomach, esophagus, and gastroduodenal junction in the rat fetus of gestational age of 17 days. In the 20-day fetus, specific binding was found in the gastric mucosa, antral circular muscle, and pyloric sphincter. Mucosal binding declined during postnatal development and had disappeared by day 15. Antral binding declined sharply between day 10 and day 15 and disappeared by day 50. Pyloric muscle binding was present in fetal stomach and persisted in the adult. Pancreatic CCK binding was not observed before day 10. These results suggest that CCK may have a role in the control of gastric emptying and ingestive behavior in the neonatal rat.

Gastric Emptying of Nondigestible Solids in the Fasted Dog

Gastric emptying of nondigestible solid particles was studied in the fasted dog. Particles of varying sizes (0.5–6.4mm), density (0.5–2.9 gm/cm3), and surface characteristics were coadministered orally with 50mL of saline and collected from a permanent duodenal cannula implanted ∼15cm from the gastroduodenal junction. The phase of the motility pattern was ascertained by the appearance of bile, which occurs during phase II, as well as by mucus discharge, which stops at the onset of phase I. A lag phase, due to the ‘quiet’ phase I, was observed in the gastric emptying of coadministered saline. This is in contrast with gastric processing of large volumes (i.e., >200mL) which can usually be approximated by first-order discharge. Most coadministered saline was discharged before the solid particles. The pH of the duodenal effluent was elevated ~1pH unit during mucus discharge and its pH can be as high as 8.3. In the fasted dog, gastric emptying of nondigestible particles closely followed the gastric motility patterns. The onset of discharge of the particles correlated with the late phase II and the phase III activity. Except for a few cases, which took two migrating motor complexes (MMC), ~90% of administered particles was discharged from the stomach after one MMC. The discharged particles were entrapped within mucous plugs. In the fasted state, gastric emptying of nondigestible particles appeared to be independent of size, density, and surface characteristics. Mucus seems to play a significant role in the distribution and discharge of the administered particles.

Physiological characteristics of ovine pyloric sphincter.

A special probe was validated to record in situ pyloric sphincter activity by changes in fiber-optic light transmission and sleeve pressure associated with the propagation of antroduodenal contractions, the onset of the phase of regular spiking activity (RSA) of the migrating myoelectric complex, the RSA-like events elicited by duodenal acidification, and the pharmacological stimulation of the gastroduodenal junction. Rapid changes in light transmission associated with antroduodenal contractions were super-imposed on slow variations, suggesting the existence of both phasic and tonic components in pyloric sphincter activity. The phasic activity coincided with isolated closures of the pyloric orifice, closures associated with antral or duodenal bulb contractions, and with long-lasting rhythmic closures during the development of the RSA phase. The resting tone increased during antral and/or duodenal stimulation and by feeding "appetizers" but decreased during antroduodenal quiescence and at the onset of general anesthesia. It is concluded that the ovine pylorus predominantly exists in a state of low resting tone but can act as a true sphincter with both inherent tonic and phasic activity.

Pharmacology of the ruminant gastroduodenal junction.

The following aspects of the pharmacology of the ovine gastroduodenal junction are reviewed: 1 The duodenal brake; 2 Cholinergic stimulation and therapy of gastric stasis; 3 Delayed gastric emptying; 4 Drugs affecting the cyclical activity of the junction.

Cell-specific immunohistochemical localization of a cellular retinol-binding protein (type two) in the small intestine of rat.

One of us recently has reported the purification of a new retinol-binding protein that is distinctly different from the well-known cellular retinol-binding protein, CRBP. This protein, which we propose to name cellular retinol-binding protein type II [CRBP(II)], was found almost exclusively in the small intestine of the adult rat at levels 1000 times greater than that of CRBP. Here we have determined the cellular location of these two proteins in the small intestine of the rat. By using an immunohistochemical technique, the absorptive cells of the small intestine, from the duodenum to the ileum, were strongly stained when antiserum against CRBP(II) was used. More intense staining was observed in absorptive cells near the tips of the villi than in those located at the base of the villi. However, the proliferative cells in the crypts of Lieberkühn were stained only lightly if at all. In contrast to absorptive cells, goblet cells in the villi did not stain. When tissue sections containing the gastroduodenal junction were examined, no staining was observed in the gastric epithelium, while the epithelium of the most proximal portion of the duodenum showed very strong staining. In tissue sections containing the ileocecal junction, staining terminated abruptly at the end of the distal ileum. No staining was observed in the epithelium of the colon. In contrast, the cellular location of CRBP in the small intestine was quite different from the cellular location of CRBP(II). The epithelial cells of the small intestine showed no staining when affinity-purified anti-CRBP was used. Staining was observed for connective tissue cells in the lamina propria and in cells located within the gut-associated lymphoid tissue. The cell-specific localization pattern determined for these two proteins suggests that CRBP(II), rather than CRBP, is the protein that plays a role in the absorption of retinol.