The peptide hormone xenin induces gallbladder contractions in conscious dogs

Xenin is a 25-amino acid peptide isolated from human gastric mucosa. The biological activities of xenin include modulating intestinal motility and affecting exocrine pancreatic secretion and gastric acid secretion. The physiological effect of xenin on the gastrointestinal tract, however, is incomplete. The objective of this study is to investigate the effects of xenin on the gastrointestinal tract motility of conscious dogs. Gastrointestinal tract and gallbladder contractions were monitored by chronically implanted force transducers. Synthetic xenin was injected intravenously during the interdigestive state with or without pretreatment with cholinergic blockers. The effects of xenin following cholecystectomy and truncal vagotomy were also investigated. Xenin induced gallbladder and jejunal contractions, although a dose-dependent response was shown only with gallbladder contractions. These effects were inhibited by pretreatment with cholinergic blockers, but were not enhanced by truncal vagotomy. The jejunal contractions were completely inhibited by cholecystectomy. The only direct effect of xenin in terms of gastrointestinal motility was to induce gallbladder contractions in conscious dogs. The neural pathway mediating xenin's action was cholinergic, but not the vagal. This novel finding indicates a new role of xenin.     

Mechanisms underlying duodeno-gastric reflux in man

BACKGROUND: Recent studies suggest that duodeno-gastro-oesophageal reflux (DGER) contributes to the occurrence of reflux oesophagitis and Barrett's oesophagus. The mechanisms underlying duodeno-gastric reflux (DGR), a prerequisite for DGER, are poorly understood. AIMS: To study the occurrence of DGR in relation to interdigestive and postprandial gastroduodenal motility. SUBJECTS AND METHODS: Ten healthy subjects underwent stationary gastroduodenal manometry with simultaneous duodenal and antral Bilitec recording 4 h before and 5 h after ingestion of a liquid meal. Eight volunteers underwent the same study, with administration of erythromycin postprandially. RESULTS: During the interdigestive phase II, all volunteers had short DGR episodes. Postprandially, DGR occurred in all subjects, on average 39 +/- 28 min after the start of the meal, and was cleared from the stomach after 242 +/- 23 min. Induction of increased antral motility and of a premature phase III, by administration of erythromycin, was associated with faster gastric DGR clearance. However, there was no direct temporal relationship between erythromycin-induced gastric phase III and erythromycin-induced DGR clearance. CONCLUSION: In healthy subjects, duodenogastric reflux occurs sporadically in the interdigestive state and is a normal phenomenon in the postprandial period. Erythromycin induces faster clearance of DGR from the stomach, which depends on enhanced antral contractile activity rather than premature phase III.     

Effects of motilin on human interdigestive gastrointestinal and gallbladder motility, and involvement of 5HT3 receptors.

A plasma motilin peak and a partial gallbladder emptying precede the antral phase III of the migrating motor complex (MMC). To clarify the causal relationship between these factors, we aimed to study the role of motilin in interdigestive gastrointestinal and gallbladder motility simultaneously. In addition, involvement of 5HT3 receptors in the action of motilin was studied. Eight fasting, healthy male volunteers received 13Leu-motilin or 0.9% NaCl i.v. for 30 min, in randomized order on two separate occasions, from 30 min after phase III. Seven of the eight subjects also received the 5HT3 receptor antagonist ondansetron in addition to motilin, on a third occasion. Antroduodenal motility, gallbladder volumes and plasma motilin were measured. The interval between the start of infusion and phase III was 95.0 (57.6-155.7) min for saline, 28.7 (21.0-33.2) min for motilin, and 39.3 (30.7-100.5) min for motilin + ondansetron (P < 0.05). Gallbladder volume decreased by one-third from 10 min after both motilin and motilin + ondansetron infusion (P < 0.05), and returned to baseline with duodenal passage of phase III. In two of the seven subjects phase III was absent after motilin + ondansetron, although gallbladder volume decreased and only refilled during a later spontaneous phase III. We conclude that motilin induces both partial gallbladder emptying and antral phase III. Indeed, although gallbladder emptying clearly precedes antral phase III, ondansetron only prevented phase III in some cases and had no effect on gallbladder emptying. Passage of phase III in the duodenum makes an important contribution to gallbladder refilling.     

The effect of cholecystectomy on duodenojejunal motility in humans

We hypothesized that certain gastrointestinal symptoms following cholecystectomy could be explained by motor disturbances. To test this hypothesis, we compared pre- and post-operative motor patterns between symptomatic and asymptomatic patients after surgery to evaluate whether some motor changes could be induced by gallbladder removal and associated with symptoms. Twenty-three patients were prospectively evaluated before and 3 months after cholecystectomy. After surgery, 17 patients were asymptomatic and six were symptomatic. Duodenojejunal manometric recordings were performed for 3 h during fasting, then 3 h after a 750-kcal meal. Patient motor results were compared to those obtained in the duodenojejunum of 20 healthy controls. After surgery, only a few modifications in duodenojejunal motility were observed compared to the preoperative period. Motor changes related to cholecystectomy were increase in phase III amplitude and the absence of progressive decrease of the duodenojejunal motor response after the meal. After surgery, symptomatic patients had a lower postprandial duodenal motility index after the meal than asymptomatic patients (P < 0.03) and more frequent propagated clusters of contractions (PCCs) (P < 0.02). Preoperative motor patterns associated with postoperative symptoms were postprandial only and included a low duodenal motility index (P < 0.03), and a higher number of PCCs (P < 0.02). Removal of the gallbladder has a limited effect on duodenojejunal motility. Few motor differences existed between symptomatic and asymptomatic patients after surgery. However, a low duodenal motor response to a meal and PCCs were often associated with symptoms.     

Intragastric acidification inhibits motilin-induced phase III activity in humans

In a randomized, placebo-controlled crossover design we studied the effect of gastric acidification on motilin-induced interdigestive antropyloroduodenal motility. Ten healthy volunteers participated in the study consisting of four experiments. Each experiment started after a spontaneous occurring phase III and consisted of intragastric infusion of either saline or acid (0.08 mol L(-1) HCl) for 90 min and intravenous infusion of either saline or motilin (4 pmol kg(-1) min(-1)) for 30 min. Antropyloroduodenal motility and pH were recorded continuously for 240 min. Reoccurrence of phase III was significantly (P < 0.05) earlier during intragastric saline-intravenous motilin infusion compared with control (intragastric saline-intravenous saline), 52 min (range 25-79) and 113 min (84-141) respectively. This effect was completely abolished during intragastric acid-intravenous motilin infusion, 112 min (82-142). The percentage of phase III of antral origin was significantly (P < 0.05) higher during intragastric saline-intravenous motilin infusion (90%) compared with control (30%). The mean area under the contraction (AUC) for phase II was significantly (P < 0.05) lower during intragastric saline-intravenous motilin infusion and intragastric acid-intravenous saline infusion compared with control. It is concluded that in humans intragastric acidification inhibits the effect of motilin on antroduodenal motility, decreases the AUC of antral phase II contractions and delays the occurrence of phase III of the migrating motor complex.     

Postprandial peristalsis in the human duodenum

MMC-related retroperistalsis is a cyclical phenomenon in the duodenum linked to phase III. The aim of this study was to elucidate the direction of propagation of juxtapyloric duodenal pressure waves in the postprandial state in healthy humans and to compare with the contractions in the interdigestive phase II. Antroduodenal manometry was performed in 11 healthy subjects. Individual pressure waves propagating along a 6-cm duodenal segment were analysed with respect to the proportions of antegrade and retrograde propagation in the four duodenal subsegments (D1–D2) to (D4–D5), each subsegment being 15 mm. A test meal was given 30 min after a phase III had passed and motility recording continued for 60 min after the meal. During both the first and the second 30-min period of postprandial recording the proportion of retrograde pressure waves was larger just distal to the pylorus, (D1–D2), 40% (23–68) and 50% (23–68), respectively, compared to the distal part, (D4–D5), of the duodenal segment, 29% (12–30) and 10%(10–24), respectively (P < 0.05 and 0.01). In contrast, during late phase II of the interdigestive state antegrade pressure waves predominated in all four duodenal subsegments. We conclude that in the postprandial state a high proportion of the duodenal pressure waves (40–50%) is retrograde in the immediate juxtapyloric area while antegrade contractions predominate at a distance 5–6 cm distal to the pylorus. These manometric data together with recent observations of postprandial transpyloric liquid flow, indicate that retrograde duodenogastric propelling of contents may be an important determinant for the gastric emptying rate.     

Human postprandial gastric emptying of indigestible solids can occur unrelated to antral phase III

According to animal experiments, postprandial gastric emptying of indigestible solids is mainly related to the antral phase III activity of the migrating motor complex. Gastric emptying of indigestible solids in humans has not been directly correlated to pressure recordings. The aim of the present study was to investigate the postprandial emptying pattern of indigestible solids in humans and its relation to fed and fasted antral motility. Ten healthy volunteers participated. After an overnight fast they had a standard breakfast. Two sizes of radiopaque markers (ROMs) were given with the test meal; ten cubes each of side measurement 1.5 mm and 3 mm, respectively. Emptying of the ROMs from the stomach was followed by fluoroscopy with simultaneous antral manometry. In six of the subjects, fasting antral manometry was performed on one day and on another day, the emptying of 7 mm cylindrical particles together with 3 mm cubes, in the absence of a gastric tube was recorded. All ROMs were emptied within 5 h (range 1.5-4.5 h). In all subjects, the smaller particles (1.5 mm) showed a slight, insignificant tendency to move from the stomach more rapidly than the larger (3 mm) particles. None of the subjects had an antral phase III before all ROMs were emptied from the stomach. Instead, the typical irregular postprandial pressure activity was present in all subjects until the emptying was completed. Furthermore, the highest postprandial motility index during the emptying study was far below the motility index during phase III, but comparable to the motility index during late phase II. Emptying of the 7 mm particles occurred significantly more slowly at 1.5-2.5 h, but otherwise was similar to the emptying of the smaller particles. There was no difference between emptying of the 3 mm cubes with or without the presence of the tube. Contrary to common opinion, gastric emptying of indigestible solids after a meal can occur unrelated to the antral phase III, at least up to a particle size of 3 mm and perhaps even 7 mm. These findings are of great importance for the evaluation of gastric emptying of indigestible solids, including the pharmacodynamics of orally administered drugs.     

Reproducibility of antroduodenal motility during prolonged ambulatory recording

Ambulatory recording of antroduodenal manometry is a novel technique with several advantages over standard stationary manometry recording. Although the feasibility of this technique in clinical practice has been demonstrated, reproducibility of antroduodenal motility recorded by means of ambulatory manometry has not been investigated. To test whether antroduodenal motility recorded by ambulatory manometry is reproducible, we performed two 24-h ambulatory antroduodenal manometry recordings in 18 healthy subjects according to an identical protocol with a 1-week interval. Motility was recorded with a five-channel solid-state catheter. Postprandial motility was recorded after consumption of two test meals and interdigestive motility was recorded nocturnally. Postprandial antroduodenal motor characteristics were identical between the separate recordings. The number and duration of nocturnal cycles of the interdigestive migrating motor complex were also in the same range. Phase III characteristics in general were not different between the two recordings. Only minor alterations were observed in the duration of phase III motor fronts with duodenal onset and in the number of interdigestive cycles concluded by duodenal onset phase III. Parameters obtained by qualitative analysis were comparable between the two recordings. The antroduodenal motility pattern, when measured by ambulatory recording with solid state catheters under standardized conditions, is very reproducible.     

Influence of naloxone on gastric emptying of solid meals, myoelectrical gastric activity and blood hormone levels in young healthy volunteers

There is considerable evidence that opioid mechanisms are involved in the mediation of pyloric motor responses that in turn regulate gastric emptying. The purpose of this randomized, placebo-controlled crossover study was to investigate the effect of naloxone on gastric emptying of a solid meal, gastric myoelectrical activity and the postprandial release of gastrointestinal peptides and neuropeptides in 20 healthy volunteers. Naloxone was administered as an intravenous bolus, followed by continuous infusion according to an intravenous dosing nomogram. Gastric emptying time was evaluated by scintigraphy and gastric myoelectrical activity was evaluated by cutaneous electrogastrography. Naloxone did not significantly alter gastric half-emptying time and postprandial dominant gastric electrical frequency compared with placebo. It also did not significantly change the plasma levels of several peptide hormones with the exception of neuropeptide Y, which was significantly increased (P = 0.001). In conclusion, in doses that influence human intestinal motility, naloxone had no effect on gastric motility and release of several peptide hormones in healthy male volunteers. The importance of the isolated increased neuropeptide Y plasma level needs further investigation.     

Acute intraduodenal bile salt depletion leads to strong gallbladder contraction, altered antroduodenal motility and high plasma motilin levels in humans.

Cholecystokinin is the main hormone involved in postprandial gallbladder contraction. There is also considerable gallbladder contraction in the fasting state, associated with phase III of the gastrointestinal migrating motor complex and release of the hormone motilin. It has been proposed that intraduodenal bile salts exert a negative-feedback control on postprandial cholecystokinin release and resulting gallbladder contraction. We wanted to elucidate whether a similar control mechanism on gallbladder contraction exists in the fasting state. We therefore performed gallbladder ultrasonography and 24-h antroduodenal motility registrations and determined plasma cholecystokinin and motilin levels in six healthy subjects before and after acute (4 g) and chronic (8 days; 8 g day(-1)) oral cholestyramine. Acute cholestyramine strongly decreased gallbladder volumes and increased motilin without changed cholecystokinin levels. There was a negative relationship between gallbladder volumes and plasma motilin levels. Although there was a persistent fasting pattern of antroduodenal motility, its cycle length was increased (P < 0.03) with markedly longer phase II (P < 0. 005). Fasting gallbladder volumes 24 h later were still strongly decreased but gradually increased to pretreatment levels. Before and after 8 days cholestyramine, interdigestive and postprandial gallbladder emptying, intestinal migrating motor complex and hormone levels did not differ. We conclude that acute (but not chronic) intraduodenal bile salt depletion with cholestyramine affects gallbladder and antroduodenal motility, possibly partly related to motilin release.     

Effects of duodenal flow on interdigestive patterns of small bowel myoelectric activity

Factors regulating the conversion of the interdigestive migrating motor complex (MMC) to postprandial patterns of motility are not completely understood. This study assessed the effects of varying rates of nonnutrient duodenal flow on patterns of interdigestive motility before and after abdominal vagotomy. Six neurally intact dogs were prepared with serosal intestinal electrodes and a duodenal infusion catheter. After recovery, the dogs were studied by infusing an isosmolar, noncaloric, balanced electrolyte solution at rates of 0, 3, 6, 9, or 12 ml/min for 5 hours into the proximal duodenum. With increasing rates of duodenal infusion, the duration of phase I decreased progressively (P < 0.05), while the period of the MMC remained unchanged. The MMC was eventually inhibited at rates of 9 or 12 ml/min with establishment of a pattern of intermittent spike activity. These findings were similar in 3 of these dogs after transthoracic total abdominal vagotomy. Our findings suggest that increases in duodenal infusion rate, independent of caloric or nutrient content, modulate patterns of intestinal motility during the postprandial period; this effect does not appear to be vagally mediated.     

The Rectal Motor Complex

To identify patterns of motility in the rectum of humans during the day while awake and at night during sleep, and to correlate the patterns with interdigestive duodenal motor complexes and sleep cycles, intraluminal rectal pressure was recorded in 12 healthy subjects (five female, seven male; mean age, 28 years) using a flexible, noncompliant, silastic catheter and an Arndorfer system with a single perfused rectal port 6 cm above the anorectal junction, duodenal motility was recorded via a perfused oroduodenal tube, and sleep stages were determined electroencephalographically. Discrete bursts of rectal motor waves, called rectal motor complexes (RMCs), were identified on 72 occasions in 11 of the 12 subjects during 157 hours of recording. The RMCs were found in daytime during fasting or after feeding (0.2 ± 0.1 RMCs/hour), but were more easily and frequently identified at night during sleep (0.8 RMCs/hour, p < .01). The complexes had a distinct onset, a mean duration ± SEM of 9.5 ± 1.0 minutes, and a distinct decline. Within each complex, the waves had a mean frequency of 3.8 ± 0.3 per minute and a mean amplitude of 19 ± 2.7 mm Hg. Complex-to-complex intervals at night averaged 74 ± 15 minutes. No clear-cut temporal association was present between the complexes and phase III of interdigestive duodenal motor complex or the REM stage of sleep.     

Gastric myoelectrical and antroduodenal motor activity in patients with achalasia

Achalasia is a primary motor disorder of the oesophagus, in which the myenteric plexus is involved. However, abnormalities in other parts of the digestive tract have also been described in achalasia. Whether gastric myoelectrical and duodenal motor activity in these patients is also affected is unknown. Therefore, interdigestive and postprandial gastric myoelectrical and antroduodenal motor activity were studied in 11 patients with achalasia, using electrogastrography (EGG) and stationary antroduodenal manometry.
Electrogastrographically, no differences were found in the gastric frequency, incidence of dysrhythmias and postprandial/fasting power ratio. In the interdigestive state a lower propagation velocity of phase III episodes was found in the achalasia patients, but other parameters were unaltered. Postprandially, no differences were found in the number of pressure waves, in the amplitude of pressure waves or in antro-duodenal coordination.
We conclude that gastric myoelectrical activity and antral motor activity in patients with achalasia is normal, suggesting an intact extrinsic and intrinsic neural innervation of the distal stomach. Although postprandial duodenal motility is normal, a lower propagation velocity of phase III suggests involvement of the small intestine in achalasia.     

Independent cycles of exocrine pancreatic secretion, hormones and gastroduodenal motility in healthy fasting humans: reassessment of a complex partnership

Background: interdigestive pancreatic secretion cycles in close association with the phases of the migrating motor complex (MMC) and release of regulatory hormones. The extrinsically denervated pancreas exhibits an intrinsic cyclic rhythm. We hypothesized that this intrinsic rhythm is normally present in the intact human pancreas. Methods: 19 healthy males (age range 26–35 years) were studied after 12 h fasting. A manometry catheter was positioned with four pressure ports in the antrum and three in the duodenum, and motility was recorded for a complete MMC cycle or 5 h. Duodenal aspirates were sampled at 15-min intervals, and immediately analysed for amylase, lipase and chymotrypsin activities; enzyme outputs were calculated by standard marker perfusion techniques. Plasma levels of pancreatic polypeptide (PP) and motilin were also determined (RIA) at 15-min intervals. Results: output of amylase, lipase and chymotrypsin occurred in parallel. All phase III motility fronts were accompanied by a pancreatic secretory peak. However, in 12 subjects at least one secretory peak was observed without the concomitant occurrence of phase III. A total of 16 out of 51 secretory peaks identified across all subjects were independent (31%). These phase III-independent peaks of pancreatic secretion occurred in subjects with a longer MMC cycle (160 ± 19 min vs 102 ± 13 min, P < 0.05). Phase III-associated and -independent peaks had a similar magnitude (amylase output: 21.6 ± 3.9 kU h⁻¹ vs 21.1 ± 2.8 kU h⁻¹, respectively). Irrespective of MMC phases, antral but not duodenal motor activity was closely correlated with fluctuations of pancreatic secretion (P < 0.05). Cycling of PP and motilin were also closely coordinated with pancreatic enzymes, with a particularly tight link between endocrine and exocrine secretion from the pancreas. Conclusions: peaks of pancreatic secretion invariably occur when a phase III motor activity occurs, but additional secretory peaks occur without a concomitant phase III. Interdigestive phasic pancreatic secretion is tightly coordinated with PP and motilin release as well as with antral motor activity. An intrinsic rhythm of the pancreas distinct from other cyclic activity may be present in healthy humans, expressed as peaks of pancreatic secretion independent of a motor phase III.     

Sham feeding disrupts phase III of the duodenal migrating motor complex in humans

The role of the vagus nerve in the control of the intestinal migrating motor complex (MMC) is unclear. This study aimed to evaluate the effect of physiological vagal stimulation with sham feeding on phase III of the MMC. Antroduodenal motility was recorded in six healthy volunteers. The first phase III was used as a control, and sham feeding was performed during the second phase III. The MMC was disrupted within 1.5 ± 0.4 min of sham feeding and its duration was shorter than the control phase III. Phase III propagation was inhibited in all subjects, most of them exhibiting no propagation beyond the third duodenal recording site. During sham feeding, the antrum exhibited transient phasic contractions in five out of six subjects. The duodenal motility index recorded for up to 30 min after the onset of the sham feeding was unchanged in five out of six subjects. We conclude that sham feeding consistently interrupted phase III of the duodenal MMC and induced antral contractions, but failed to provoke significant motor events in the duodenum.     

Manometric responses of human duodenum during infusion of HCl,hyperosmolar saline,bile and oleic acid

Abstract Duodenal motor activity is incompletely understood. The purpose of this study was to define the contractile patterns of the duodenum that occur in response to rate controlled injection of various solutions. In nine healthy volunteers we placed a six channel perfused catheter, and recorded pressure activity in the antrum, pylorus and duodenum. Volumes of 10 and 20 mL of 0.9% NaCl, 100 mM HCl (pH 1), 5% NaCl (1711 mOsm/kg), human bile and iso-osmolar sodium oleate were randomly injected into the duodenum at 20 ml/min, starting IS min after phase III migratory motor complex (MMC). A 20 mL bolus of each solution caused more activity (P < 0.05) than a 10 mL bolus, but the motor pattern was similar. The control, 0.9% NaCl, produced occasional pressure waves, whereas bile and sodium oleate induced more (P < 0.05) activity which consisted of low amplitude, isolated or clusters (2–4 cycle/min) of non-propagating pressure waves that occurred at random sites. In three subjects, oleate produced isolated pyloric phasic contractions. In contrast, HCl and 5% NaCl induced high amplitude pressure waves that were seen either at a single channel or at multiple channels, occurring simultaneously. The motility index was also greater (P < 0.05) than that induced by other solutions. Additionally, within 2 min of infusion, a phase III MMC like pattern was observed in five of the nine subjects who received HCl and three of the nine who received 5% NaCl. A non-nutrient iso-osmolar solution induced occasional motor activity. HCl and hyperosmolar solutions induced more frequent and large amplitude, segmental contractions whereas lipid and bile induced fewer and smaller amplitude contractions. The volume, the pH, the osmolar and the nutrient make up of the infusate may each influence the duodenal motor responses.     

Postprandial duodenojejunal motility in health and idiopathic severe gastroparesis: from conventional analysis to nonlinear dynamics analysis.

Our aim was to compare the results of the analysis of postprandial duodenojejunal motor patterns provided by a conventional computer-aided analysis with those provided by the new nonlinear mathematical method borrowed from 'chaos theory for determining how nonlinear analysis can improve fed motor pattern analysis and detect organization of postprandial contractions. Ten patients who had been explored for an idiopathic gastroparesis, and 20 healthy volunteers underwent duodenojejunal manometric recording for 3 h after a 750 kcal meal. Computer-aided analysis on each half-hour of the postprandial recording period calculated the number of waves (NW) and the area under the curve (AUC). Pressure signals were concurrently described by phase portraits obtained by plotting each pressure value at time t with the pressure value at time t + 1 s. The shape and amplitude of phase portraits were visually analysed and the relative area covered (RAC) by the phase portraits was calculated. With conventional analysis, NW and AUC were maximal during the first post-meal hour then decreased with time both in healthy volunteers and gastroparetic patients. With this analysis, the only difference between patients and controls was a lower NW (P < 0.02) in patients, observed only in the duodenum. Phase portraits analysis demonstrated lower RAC, a different distribution of RAC and more regular phase portraits in patients than in controls. Phase portraits outlined the heterogeneity of the patient group contrasting with the homogeneity of the control group when no subgroup was demonstrated by conventional analysis. We therefore conclude that the study of post prandial duodenojejunal motor behaviour could be improved by nonlinear dynamic analysis.     

GLP-1 regulates gastroduodenal motility involving cholinergic pathways

Abstract  The gut-born incretin hormone glucagon-like peptide-1 (GLP-1) delays gastric emptying. To elucidate the mechanisms by which GLP-1 affects gastroduodenal motility and glycaemia, we studied the effects of exendin(9–39), a potent GLP-1 receptor antagonist, on gastroduodenal motility and pancreatic hormones. In this randomized, double-blind, placebo-controlled, four-arm, cross-over trial, 10 healthy volunteers were studied during the interdigestive period followed by duodenal perfusion of a mixed liquid meal (250 kcal). On four separate days, exendin(9–39), atropine, exendin(9–39) + atropine or saline were infused intravenously. Antro-pyloro-duodenal and fundic motility were assessed. The compliance of the proximal stomach was determined by isobaric distensions. During fasting, exendin(9–39) did not influence proximal gastric volume, pyloric tone, and duodenal contractility. Exendin(9–39) significantly increased antral waves only in the absence of atropine. During duodenal meal perfusion, exendin(9–39) significantly reduced proximal gastric volume accommodation, abbreviated postprandial antral inhibition, reduced the postprandial increase in pyloric tone, and reduced gastric compliance. Atropine abolished the effects of exendin(9–39) on gastric volume accommodation but did not affect its effects on postprandial antroduodenal motility and on gastric compliance. Exendin(9–39) increased fasting and postprandial glycaemia and plasma glucagon but not insulin concentrations. Atropine did not affect GLP-1 secretion. Cholinergic mechanisms mediate the effects of GLP-1 on postprandial gastric accommodation but not on antro-pyloro-duodenal motility. GLP-1 reduces fasting and postprandial glycaemia, in part by reducing glucagon secretion.     

Evaluation of the refractory period of the human migrating motor complex through induction of premature Phase III

We examined the refractory period of the migrating motor complex and the ability of somatostatin to increase the oscillation frequency of the complex through the initiation of premature phase HI activity. Fifteen normal human subjects were studied by means of a naso-intestinal motility probe and divided in three groups of five subjects each. After recording three spontaneous migrating motor complexes, somatostatin was infused at a time interval from the last spontaneous Phase III that corresponded to 10% (Group A), 20% (Group B) and 30% (Group C) of the previous mean cycle length. Eleven successive somatostatin infusions were given with the interval between each infusion being altered in a fashion designed to identify the refractory period of the MMC. The results show a spontaneous cycle length of 121.3 ± 15.8 min (mean ± SD). When given at 10% (12 min) of the previous cycle somatostatin did not elicit any response, when given at 20% (24 min) of the cycle somatostatin induced a premature Phase III activity in three of five subjects; when given at 30% (36 min) of the cycle somatostatin induced a premature Phase III in all five subjects examined. Each somatostatin infusion was associated with the onset of a premature Phase III activity in 50% of the trials when the time interval was 20% of the ideal cycle (24 ± 4 min). When the time interval was increased to 30% of the ideal cycle a premature Phase III could be recorded after each somatostatin infusion in all trials. Motilin and pancreatic polypeptide plasma levels were significantly lowered by somatostatin. It is concluded that the migrating motor complex of the human gastrointestinal tract shows an absolute and a relative refractory state. Repetitive infusions of somatostatin for short periods may increase the occurrence of Phase III activity up to four-fold.     

The role of remote gut inflammation in duodenojejunal dysmotility

The aim of this prospective study was to determine the role of remote inflammation of the gut on duodenojejunal motor status by comparing patients with acute cholecystitis (AC) to those with biliary colic (BC). Thirty-six gallstone patients (11 AC and 25 BC) were explored. Manometric recordings were performed during fasting and after a 750-kcal meal and ended by an intravenous injection of 100 mg trimebutine. Patient data were compared to those of 20 healthy controls. Phases III were more frequently absent in AC patients than in BC patients (P < 0.01) and controls (P < 0.05). When phase III characteristics were similar between the AC and BC group, the phase III amplitude was lower in both groups than in controls (P < 0.0001). After the meal, the mean motor index in the jejunum expressed by the area under the curve (AUC) per 30-min period was higher in the AC group than in BC group and controls (P < 0.05). Specific motor phenomena were observed after the meal. In particular, propagating clusters of contractions (PCCs) were more frequent in AC patients than in BC (P < 0.05) and controls (P < 0.01). A lack of the expected decrease in the AUC during recording occurred with the same frequency in the AC and BC groups but was more frequent in patients than in controls (P < 0.05). In 8/11 patients in the AC group with duodenojejunal tracings before and 3 months after surgery, preoperative motor disturbances disappeared in 5/8 patients and improved in 3/8 patients. The higher frequency of duodenojejunal motor disturbances especially after a meal in patients with AC and their disappearance in most of the patients after removal of the infected gallbladder suggest that remote inflammation of the gut affects duodenojejunal motility.