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The neuroendocrine control of gastrointestinal motor activity.

Here we describe interactions between peptide hormones and the enteric, autonomic and central innervation, and to the regulation of some major digestive events. The neuronal functions, the variety of neurochemically distinct neurons and some recent results on chemical marker combinations in the neurons are mentioned. A classification of the substances potentially acting as neurotransmitters or neuromodulators of gut motility is also reported. The major motor events taken into account include the migrating motor complex, the peristaltic reflex, the gastric emptying and the gallbladder/sphincter of Oddi relationships. The demonstration that numerous peptides may be detected in, and secreted by, the neurons has opened a fascinating area of study. Various difficulties hampering the comprehension of modalities according to which gastrointestinal motility is regulated, are discussed. Experimental evidence however, has to be considered cautiously. Expressions such as 'the peptidergic control of motility' may suggest that these peptides are the primary subjects in the strategy leading to the motor events, rather than the transmitters of impulses whose strategy is decided at higher levels. The autonomy of the peripheral regulatory system is apparent in certain conditions and has an important supplementary value. In general, however, the neuroendocrine regulation remains a global phenomenon testifying the unity of the living organism.

Cholecystokinin↗

Antroduodenal manometry. Usefulness and limitations as an outpatient study.

We performed fasting and postprandial recordings of antroduodenal manometry in 21 normal volunteers, 13 patients with insulin-dependent diabetes mellitus and gastrointestinal symptoms, and 11 patients with the irritable bowel syndrome. None of the patients or volunteers had previously undergone an intestinal intubation study. Recordings could not be obtained from four of the diabetic patients due to failure to intubate the pylorus. Catheter migration led to incomplete antral data in a further 21% of all recordings. Due to the wide variations demonstrated by the normal volunteers, parameters of either the migrating motor complex (MMC) or the fed response could not differentiate between either of the patient groups and/or the controls. Similarly, while abnormal patterns of either fasting or postprandial motility were common in the diabetic patients, manometry had a sensitivity of only 67% in comparison to the less invasive radionuclide gastric emptying study. Furthermore, manometry failed to identify any diagnostic abnormality in irritable bowel patients; in particular, the incidence of "clustered" contractions was similar in all three groups. We conclude that short duration antroduodenal manometry is of limited diagnostic usefulness due to the difficulties in pyloric intubation in the presence of a dilated stomach and the intrinsic variability in normal motor patterns, perhaps excerbated by the stressful effects of the procedure itself in tube-naive subjects.

Adult↗

Upper jejunal motility after pancreatoduodenectomy according to the type of anastomosis, pancreaticojejunal or pancreaticogastric.

BACKGROUND: The goal of this study was to compare upper jejunal motor patterns after Billroth II pancreatoduodenectomy according to the type of pancreatic anastomosis (pancreaticojejunostomy [PJA] or pancreaticogastrostomy [PGA]) and the presence or absence of postoperative symptoms. STUDY DESIGN: Manometric recordings during fasting and after a 750-kcal meal were performed in the afferent limb in 12 patients (7 PJA, 5 PGA) and in the efferent limb in 15 other patients (7 PJA, 8 PGA) with a postoperative delay of 15+/-6 days and 3.9+/-2.2 months respectively. Patient data were compared to those of 20 healthy controls. RESULTS: During fasting, the 2 main abnormal findings were a higher incidence (p < 0.05) and a slower migration velocity (p < 0.01) of incomplete phase III by comparison with that recorded in controls. No difference for phase III was observed between the 2 surgical procedures regardless of recording site. Trimebutine, 100 mg intravenously, induced a phase III in 89% (24 of 27) of the patients. Delay of motor response varied from 5 to 10 minutes without difference between the recording site; it was less than 2 minutes in 100% of controls. Trimebutine-induced phase III showed similar propagation abnormalities to the spontaneous phase III. Duration of the fed pattern (p < 0.001) and motor index (p < 0.001) were significantly lower than in controls after the meal, in both limbs, whatever the type of anastomosis. Differences between the 2 surgical procedures were a slower migration velocity of phase III (p < 0.01) and a lower postmeal motor index (p < 0.05) in the efferent limb after PJA than after PGA. Nine of 27 patients were symptomatic. In these 9 patients, mean phase III migration velocity was slower (p < 0.001), and mean area under the postprandial curve was higher (p < 0.01) than in asymptomatic patients. Propagated clusters of contractions were only found in symptomatic patients and in the afferent limb. CONCLUSIONS: Pancreatoduodenectomy is associated with significant motor disturbances, mainly slower phase III and a reduced fed pattern, in the upper jejunum, at least during the first 3 postoperative months. Few motor differences were observed between PGA and PJA pancreatic anastomosis. A lesser occurrence of postsurgical motor anomalies does not appear to be an argument for preferring PGA to PJA.

Aged↗

Interdigestive cycling in chronic pancreatitis: altered coordination among pancreatic secretion, motility, and hormones.

BACKGROUND & AIMS: Secretions from the exocrine and endocrine pancreas may modulate interdigestive motility. To test this hypothesis in humans, we investigated interdigestive cycling in patients with chronic pancreatitis (CP) as a model of impaired pancreatic function. METHODS: Antroduodenal motility, pancreatic enzyme output, and pancreatic polypeptide release were monitored for two consecutive interdigestive cycles in 13 controls and 9 patients with CP. RESULTS: Interdigestive enzyme output was severely impaired in patients with CP (> 80% decrease); however, secretory cycling was still evident in most patients. All parameters describing interdigestive motility were similar in controls and patients with CP (duration of the migrating motor complex [MMC] was 107 +/- 19 minutes in patients with CP vs. 114 +/- 15 minutes in controls). The time between cyclic peaks of enzyme secretion (76 +/- 4 minutes vs. 101 +/- 4 minutes in controls) and pancreatic polypeptide (63 +/- 4 minutes vs. 106 +/- 7 minutes in controls) was shortened in patients with CP, and peaks were no longer temporally related to the MMC. Only 56% of phase III activity fronts were associated with a concomitant secretory peak in patients with CP compared with 92% in healthy subjects. CONCLUSIONS: CP not only decreases pancreatic secretion but interrupts the coordination among interdigestive cyclic phenomena. Our findings in several animal and human models refute the concept that pancreatic mechanisms exert a major regulatory influence on interdigestive motor activity.

Adult↗

Gender influence on jejunal migrating motor complex.

The role of gender and the menstrual cycle in small bowel motility has not been clearly elucidated. Jejunal motility was recorded with a nasojejunal catheter incorporating five solid-state pressure transducers in ambulatory menstruating women and men of comparable age over 24 h. All women were studied twice, in the early follicular (early-F) and midluteal (mid-L) phases of the menstrual cycle, verified by determining serum levels of gonadal steroids and gonadotropins. The propagation velocity of phase III was slow and the contraction amplitude was high in both menstrual cycle phases compared with men, and these parameters were correlated with serum estrogen levels in the mid-L phase. In the early-F phase, migrating motor complex (MMC) cycle duration during sleep was long compared with other groups and positively correlated with estrogen concentrations, whereas in the mid-L phase MMC cycle duration during sleep was negatively correlated with serum progesterone levels. In all groups, the frequency of phase III contractions was low and the intercontractile interval measured from pressure peak to peak was long during sleep compared with the awake state. Postprandial motility did not display gender difference in any parameter examined. The results demonstrate that the majority of patterns of motility are similar in menstruating women and men, whereas certain aspects of the MMC, most conspicuously propagation velocity and phase III contraction amplitude, differ. We have also documented circadian variation of phase III contraction frequency in both women and men.

Adult↗

Effects of proximal duodenal transection and anastomosis on interdigestive sphincter of Oddi cyclic motility in conscious dogs.

Gallstones formed after gastrectomy are bilirubinate stones probably associated with biliary stasis and infection. Effects of proximal duodenal transection performed during gastrectomy on interdigestive sphincter of Oddi cyclic motility possibly relevant to this phenomenon were investigated in four conscious dogs. Although the cyclic change in sphincter motility was still in concert with the duodenal migrating motor complex after duodenal transection, the mean period was shortened (p < 0.02), and the frequency (p < 0.005) and amplitude (p < 0.001) of sphincter phasic waves during phase III were decreased. The cyclic variation of basal pressure disappeared, and the mean basal pressure throughout the cycle was significantly reduced (p < 0.003). Transient inhibition of sphincter and duodenal contractions normally seen during phase III disappeared. Duodenal transection reversed the response of the sphincter to cholecystokinin-octapeptide from inhibition to stimulation and from reduction of the basal pressure to elevation. These data suggest that duodenal transection produces significant changes in interdigestive sphincter of Oddi motility, possibly contributing to augmented duodenobiliary reflux and then lithogenesis. Myoneural continuity between the stomach and sphincter of Oddi at the proximal duodenum may play an important role in maintaining normal biliary dynamics.

Anastomosis, Surgical↗

Relationship between jejunal interdigestive migrating motor complex and quality of life after total gastrectomy with Roux-en-Y reconstruction for early gastric cancer.

A total of 22 patients (16 men, 6 women; age 33 to 70 years, m mean, 60.2 years) 1.0 to 1.5 years (mean 1 year and 2 months) after total gastrectomy with Roux-en- Y reconstruction for early gastric cancer (D2 lymph node dissection, curability A) were divided into two groups based on the occurrence of interdigestive migrating motor complex, phase III (IMMC-pIII) from the Roux-en- Y loop, and postoperative quality of life (QOL) was compared. Results were as follows: (1) Patients in the IMMC- pIII positive group (n = 12) had more appetite and ate more food with less decrease in body weight than those in the IMMC-pIII negative group (n = 10). (2) Patients in the IMMC-pIII positive group clearly had fewer symptoms, such as early dumping symptoms (systemic symptoms), symptoms of reflux esophagitis (e.g., heartburn, feeling of regurgitation, difficult swallowing), nausea, abdominal pain, diarrhea, abdominal fullness, and borborygmus, than those in the IMMC-pIII negative group. These results showed a more satisfactory condition in regard to abdominal symptoms in the IMMC-pIII positive group than in the IMMC-pIII negative group.

Adult↗

Effect of iron succinyl-protein complexes on gastrointestinal motility in the fasting dog.

Studying the gastrointestinal motor effects of iron compounds may help to elucidate the mechanism originating the gastrointestinal side effects of frequently reported during martial therapy. The aims of the present study were: (1) to examine the gastrointestinal motor effects of ferrous sulfate (reference compound) and (2) to compare its effects with those of two iron succinyl-protein complexes (ITF 1096 and ITF 282, an iron-albumin and iron-casein complex, respectively). In 6 fasting, conscious dogs, fitted with 8 bipolar electrodes and 3 strain-gauge force transducers along the gastrointestinal tract, gastrointestinal motor activity was recorded. Ferrous sulfate and iron succinyl-protein complexes were administered by an orogastric tube at two dose levels: the lower and higher dose levels were approximately equivalent to 10 and 30 mg/kg as Fe, respectively. In control experiments, 154 mM NaCl, ITF 211 (succinylated albumin) and ITF 297 (succinylated casein) were used. Administration of 154 mM NaCl did not affect gastrointestinal motility nor did it disrupt migrating motor complex (MMC) cycling. ITF 1096 and ITF 282, only at the higher dose, lengthened the MMC period and increased intestinal, but not gastric spike activity. The effects of ITF 211 and ITF 297 were similar to those of ITF 1096 and ITF 282. Ferrous sulfate, at the lower dose, lengthened the MMC period; the higher dose disrupted MMC cycling and induced intense, irregular spike bursts in the stomach and in the small bowel, accompanied, in 3 out of 6 dogs, by a prolonged tonic contraction of the upper small bowel. Four out of 6 dogs vomited after the higher dose of ferrous sulfate. No vomiting was observed with any of the other treatments. We conclude that ITF 1096 and ITF 282 have a markedly better gastrointestinal tolerability than ferrous sulfate.

Animals↗

Motilin controls cyclic release of insulin through vagal cholinergic muscarinic pathways in fasted dogs.

The effect of motilin on insulin release has not been studied in the interdigestive state. Adult mongrel dogs were chronically implanted with force transducers in the stomach and duodenum to monitor contractile activity, and the plasma motilin and insulin concentrations were measured by a specific radioimmunoassay and enzyme immunoassay, respectively. The concentration of insulin in plasma was found to fluctuate in close association with that of motilin and phase III of the interdigestive migrating contractions in the stomach. This spontaneous release of insulin was mimicked by intravenous infusion of motilin at a dose of 0.3 microgram.kg-1.h-1. Exogenous motilin (0.01-0.3 microgram/kg) dose dependently stimulated insulin release, which was abolished by atropine, hexamethonium, ondansetron, and truncal vagotomy. Phentolamine significantly enhanced, whereas propranolol inhibited, motilin-induced insulin release. In a perifusion system using islet cells from the canine pancreas, motilin did not affect insulin release. In conclusion, motilin stimulates insulin release through vagal cholinergic, muscarinic receptors on pancreatic beta-cells, and the effect appears to be modulated by adrenergic nerves.

Activity Cycles↗

Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis.

Patients with bacterial overgrowth of the small intestine developed spontaneous bacterial peritonitis (SBP) more frequently than patients without bacterial overgrowth of the small intestine. The objective of this study was to determine whether the incidences of small intestine dysmotility and bacterial overgrowth are higher in cirrhotic patients with a history of SBP than in cirrhotic patients without SBP. Forty cirrhotic patients were enrolled in this study. There were 20 patients with a history of SBP and 20 patients without a history of SBP. Small intestine bacterial overgrowth was diagnosed by breath hydrogen test. Small intestine motility was recorded, by a 3-channel solid-state manometric catheter, for 24 hours. There were no statistical differences in age or sex between the two groups. The Child-Pugh scores in the SBP group were higher than in the non-SBP group (10.5 +/- 2.1 vs. 8.1 +/- 1.9, P < .01). The incidence of bacterial overgrowth of the small intestine was higher in the SBP group than in the non-SBP group (70% vs. 20%, P < .01). The amplitude and duration of migrating motor complex (MMC) activity fronts, as well as the number of clusters per hour, were similar in both groups. However, the frequency of MMC activity fronts was higher in the non-SBP group than in the SBP group (4.8 +/- 2.3/24 hours vs. 3.5 +/- 1.2/24 hours, P < .05). In addition, the MMC velocity was significantly higher in the non-SBP group (8.3 +/- 2.6 vs. 5.3 +/- 2.1 cm/min, P < .01). The incidence of bacterial overgrowth of the small intestine was higher in cirrhotic patients with history of SBP than in those without SBP. Small intestine motility dysfunction was more severe in cirrhotic patients with history of SBP. Impaired motility of the small intestine, causing bacterial overgrowth of the small intestine, may be one of the explanations for recurrent SBP in cirrhotic patients.

Adult↗

Chyme transport patterns in human duodenum, determined by multiple intraluminal impedancometry.

To get information about the mechanisms involved in chyme transport during the fasting and postprandial states, the novel procedure of multiple intraluminal impedancometry was evaluated in 14 healthy subjects (6 during fasting, 8 after a test meal). All main features of the migrating motor complex (MMC) cycle were determined. During phase II of the MMC cycle and the postprandial period, different transport patterns of chyme, termed bolus transport events (BTEs), were determined. These were 1) simple long-distance propulsive transport (spreading distance > 16 cm), 2) short-distance propulsive transport, and 3) retrograde transport. A significantly lower number of BTEs was recorded during fasting than postprandially. Short-distance propulsive BTEs predominated during fasting (72%), and long-distance propulsive BTEs predominated after the test meal (76%). Retrograde BTEs were recorded during fasting (4%) and postprandially (8%). In the latter state, complex long-distance propulsive BTEs were also observed (5%), consisting of multiple components. A major proportion of gastric contents was found to be continuously transported to jejunum. In conclusion, impedancometry enables us to determine patterns and parameters of chyme transport during fasting and postprandial states.

Adult↗

Effects of smoking on interdigestive gastrointestinal motility.

The effect of smoking on interdigestive gastrointestinal motility is little studied but may play a role in gastrointestinal morbidity. We studied gastroduodenal motility in 10 volunteers (five smokers and five nonsmokers) using a water-perfused pressure catheter. A pH probe was placed in the duodenal bulb. Baseline motility was recorded until phase III of the migrating-motor complex had occurred in the stomach three times in order to record two complete cycles of MMC activity. Subjects then began smoking until phase III activity occurred again (mean duration of smoking 117 min). During the control period, all subjects had normal MMC cycles and there were no differences between smokers and nonsmokers. While smoking, no gastric phase III was observed in any subject and gastric motility was markedly reduced. In seven of 10 subjects, smoking did not prevent the occurrence of normal duodenal phase III activity. Three subjects had no duodenal phase III activity during smoking. The duodenal pH profile did not change during smoking and motilin levels continued to fluctuate in conjunction with phase III activity. In conclusion, smoking abolished phase III activity in the stomach without affecting the plasma motilin cyclic fluctuations or duodenal bulb pH. In contrast, smoking has little effect on duodenal motility.

Adult↗

Effects of motility on epithelial transport in the human descending duodenum.

The aim of the study was to determine how motility affects the balance between absorptive and secretory ion transport in the proximal human small intestine. Thirty-two healthy subjects and 16 patients (eight with villus atrophy, eight with normal duodenal biopsies) were studied. The absorptive sodium flux was estimated by measurement of bicarbonate absorption with a double-lumen perfusion technique. The secretory chloride flux was calculated from the ratio between the continuously recorded transmural potential difference (PD) and the epithelial parallel resistance, which was measured in forceps biopsies by square-wave current analysis. Graded variations in contraction frequency were obtained by recording during defined time periods before, during and after phase III of the migrating motor complex (MMC). Bicarbonate was absorbed by a process that led to CO2 formation, and both bicarbonate absorption and luminal PCO2 increased with contraction frequency. The motility-related PCO2 rise was reduced in patients with villus atrophy and by removal of bicarbonate from the perfusate. A higher motor activity was also associated with a larger PD (more lumen negative). Both the absorptive and the secretory fluxes were thus enhanced by motility. The estimated absorptive flux was approximately twice as large as the secretory flux during periods of low motor activity, and four times as large during submaximal motor activity. We conclude that motor activity affects both absorptive and secretory mucosal function in a quantifiable manner. Information about the behaviour of the respective linkage functions may make it possible to model the intestinal absorption process in vivo.

Adult↗

Effect of erythromycin on gastroduodenal contractile activity in developing neonates.

BACKGROUND: The occurrence of phase III of migrating motor complexes in neonates is inversely related to gestational age, and it can be triggered in some infants by the motilin receptor agonist erythromycin. After intragastric erythromycin, the authors determined 1) the occurrence and characteristics of phase III of migrating motor complexes, 2) the antral and duodenal motor responses, and 3) the dose-response relation among preterm and full-term infants. METHODS: Using an unbalanced, repeated measures design, 25 preterm and term infants were given two of three doses of intragastric erythromycin: 0.75, 1.5, and 3.0 mg/kg. Motor activity was recorded 3 hours before and 2 hours after each dose using a continuous water perfusion manometry system. RESULTS: Erythromycin failed to induce phase III of migrating motor complexes in infants younger than 31 weeks' gestation; however, it induced phase III in a dose-dependent manner among infants whose gestational ages were 32 weeks and older ( P < 0.05). Erythromycin significantly increased the amplitude and frequency of antral contractions in term infants and significantly increased the duodenal contraction amplitude in older preterm and term infants, but these effects were absent in younger preterm infants. CONCLUSIONS: The ontogenic emergence of the motilin receptor-mediated induction of phase III occurs by 32 weeks' gestation, whereas the non-motilin-mediated response of increased antroduodenal motor activity is not observed until term. Therefore, early use of erythromycin as a prokinetic agent may not be useful in very preterm infants, partially useful in older preterm infants, and useful in full-term infants.

Aging↗

Susceptibility to adenosine agonists of giant migrating contraction induced by glycerol enema in anesthetized rats.

The present study examined whether adenosine agonists influence the occurrence of giant migrating contractions (GMCs) induced by glycerol enema (65%, 2 ml/kg) in rats. Catheter pressure transducers were used to measure the colonic luminal manometric alterations. The adenosine A1 agonists (2S)-N6-(2-endo-norbornyl)adenosine ((S)-ENBA) (10 micrograms/kg, i.v.) and N6-cyclohexyladenosine (30 micrograms/kg, i.v.) abolished the GMCs, whereas the adenosine A2 agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosin e (CGS 21680) (30-300 micrograms/kg, i.v.) failed to influence the GMCs. The suppressive action of (S)-ENBA on the GMCs was entirely counteracted by the peripheral adenosine antagonist 8-(p-sulfophenyl)theophylline (10 mg/kg, i.v.). The present observations suggest that the adenosine A1 agonist suppresses the GMCs via peripheral adenosine receptors.

Adenosine↗

Relationship between acid secretory activity and gastroduodenal migrating motor complex.

BACKGROUND/AIMS: As acid secretory activity fluctuates with the same rhythm as motor activity during the interdigestive period, we investigated the relationship between these two cyclic activities. MATERIAL AND METHODS: In a series of 9 normal subjects the interdigestive gastroduodenal motor activity and the intragastric pH were recorded after an overnight fasting by means of a manometric and pH-metric apparatus. Thirty minutes after the second phase III of the Migrating Motor Complex (MMC), omeprazole, a proton pump inhibitor, was administered intravenously at a dose of 20 mg. RESULTS: After omeprazole administration, a typical gastroduodenal phase III similar to the spontaneous one appeared before its expected occurrence. The amplitude and frequency of pressure waves of the period between the end of omeprazole administration and the beginning of phase III were not significantly different from those of the period preceding the spontaneous phase III, but were significantly different from those of a corresponding period starting 30 min after a spontaneous phase III. The intragastric pH showed a significant increase from the basal values before the beginning of gastric phase III and continued to increase up to the end of recording. CONCLUSIONS: The fact that the block of gastric acid secretion is followed by the appearance of a typical gastroduodenal phase III suggests that the acid secretory activity may have some influence on motor activity of the gastroduodenal tract.

Adolescent↗

Manometric evaluation of gastrointestinal motility in children with chronic intestinal pseudo-obstruction syndrome.

Various causes of abnormal gastrointestinal motility may account for the symptoms of chronic intestinal pseudo-obstruction syndrome (CIIPS). Fasting gastrointestinal motility in humans is characterized by regular cyclic activity of the migrating motor complex (MMC), which may be used as an objective indicator of intestinal motility. The present study investigated MMC in five children with CIIPS (2 neurogenic and 3 nonneurogenic cases) using a perfused catheter system. The findings were compared with those for children with idiopathic constipation and Hirschsprung's disease. The gastrointestinal MMC was found to be abnormal with CIIPS, whereas it remained normal with idiopathic constipation and Hirschsprung's disease. The four CIIPS patients without any gastrointestinal MMC activity required total pareteral nutrition. There was significant improvement of intestinal motility over time in a patient with immaturity of ganglia, and there was gradual deterioration in a patient with hypoganglionosis. In conclusion, gastrointestinal motility studies provide objective diagnostic information in patients with intestinal dysmotility and can be used as an indicator of intestinal function during the treatment of CIIPS.

Adolescent↗

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.

Adult↗