Interdigestive Motility Research Articles

Dopamine-induced migrating myoelectrical complex-like activity in human duodenum

The effect of dopamine on human gastric and small intestinal interdigestive motility was investigated in 12 subjects. Intestinal motility was recorded by means of a four-lumen polyvinyl probe with four open tips located 15 cm apart, continuously perfused with distilled water. In each subject during the same study, after recording two consecutive spontaneous phase III of migrating myoelectrical complexes and when a phase II appeared, dopamine was infused intravenously twice in a dose of 5 micrograms/kg/min for 15 min with an interval of 20 min between each infusion. In six subjects, the second dopamine infusion was preceded by a treatment with sulpiride (10 mg, intravenously, as bolus) or domperidone (10 mg, intravenously, as bolus), each considered a highly selective dopamine antagonist. The results show that dopamine stimulates duodenal motility producing a pattern similar to that observed in phase III of spontaneously occurring migrating myoelectrical complexes. The second dopamine infusion reproduced in all cases the same pattern of motility as observed during the first infusion. Sulpiride and domperidone prevented the effect of dopamine in all cases. It is therefore suggested that dopamine-induced duodenal motility may involve specific dopaminergic receptors.

Effect of calcitonin on the interdigestive motility and on gastric and pancreatic secretion in humans

Calcitonin given in doses (0.2 and 1 MRC U/kg-1h-1) reproducing the levels observed in medullary carcinoma of the thyroid, induced the appearance of phase III type activity and reduced the duration of the IMC in the small intestine from 123 to 87 min with 0.2 MRC U kg-1h-1 and from 123 to 43 min with 1 MRC U kg-1h-1 but not in the stomach of young volunteers. This increase in phase III-like activity occurred despite a sharp reduction in motilin levels. Only the highest dose of calcitonin reduced significantly acid secretion (by more than 90%) while both doses reduced amylase secretion by respectively 65 and 71% when compared to the control levels. These changes in motility and secretion could partly explain the diarrhea observed in patients with the medullary carcinoma of the thyroid.

Interdigestive gastroduodenal motility and serum motilin levels in patients with idiopathic delay in gastric emptying

The interdigestive gastroduodenal motor activity and serum motilin levels were studied in 22 dyspeptic patients with markedly delayed gastric emptying not due to diseases known to impair gastroduodenal motility and in 7 control subjects with normal gastric emptying. Motor activity was recorded using a manometric probe positioned in the gastric antrum and in the proximal duodenum, and blood samples for radioimmunoassay of motilin were taken every 15 min during the recording period. The control subjects showed gastroduodenal activity fronts of the migrating motor complex associated with motilin peaks. Almost all patients with delayed gastric emptying showed no activity fronts in the stomach, and only half of them showed activity fronts starting in the duodenum. In these patients a significant reduction in the number of motilin peaks and in the integrated motilin output during the identified peaks was also observed. The results of this study indicate that most dyspeptic patients with idiopathic delay in gastric emptying may also have an alteration in interdigestive gastroduodenal motility, mainly characterized by a lack of gastric activity fronts, associated with an impaired motilin release.

Action of intragastric ethanol on pancreatic exocrine secretion in relation to the interdigestive gastrointestinal motility in humans

On different days, fasted volunteers were given either 100 ml of ethanol (40% v/v), glucose (isocaloric to ethanol) or distilled water intragastrically; the instillations always starting during the first observed duodenal phase I of the interdigestive migrating complex (IMC). Both ethanol and glucose produced a fed pattern of motility but only glucose significantly (P less than 0.05) delayed the reappearance of a new duodenal phase III of the IMC when compared to water. Ethanol and glucose significantly increased the 1-h duodenal bicarbonate output 7- and 16-fold, respectively. Glucose, but not ethanol, stimulated the duodenal amylase output when compared to water. Glucose, but not ethanol, caused a significant rise in plasma gastrin concentration; plasma secretin levels not being altered by both substances. We conclude that in non-alcoholic humans, an intragastric administration of ethanol in a concentration present in whisky and in an amount that is consumed in ordinary social drinking has a weak stimulatory action on pancreatic bicarbonate secretion and that this action is not mediated by release of secretin.

Effects of corticotropin-releasing factor, corticotropin and cortisol on gastrointestinal motility in dogs

Gastrointestinal motor activity following intracerebroventricular (ICV) and intravenous (IV) administration of corticotropin releasing factor (CRF), corticotropin (ACTH) and cortisol was investigated in fasted dogs with strain-gauge transducers chronically implanted on the antrum and proximal jejunum. ICV but not IV administration of CRF (20 to 100 ng/kg) suppressed the gastric cyclic migrating motor complex (MMC) for 3 to 6 hours without affecting the jejunum. Similar disruptive effects on the gastric MMC were observed after ICV administration of ACTH (0.5 U/kg) or cortisol (0.1 μg/kg) but not after IV administration of 10 times higher doses. These results suggest that in dog (1) CRF may be involved in the central control of the interdigestive gastric motility, (2) these effects were not probably due to the release of ACTH and cortisol, (3) the other hormones of the pituitary adrenocortical system change the gastric motility when centrally administered through a possible feed-back mechanism affecting brain CRF level.

A continuous manometric study of the human pylorus

Previous manometric studies of the pylorus in humans have yielded conflicting data. These interstudy variations may be the result of differences in technique. It is also possible that pyloric pressure shows cyclic variations with the interdigestive motility complex. PyJoric pressure was monitored continuously for 300 min in 6 healthy men by means of a Dent sleeve. Gastroduodenal activity was measured simultaneously by using a perfused catheter system with two antral and two duodenal ports. With this method the pylorus was shown to have no elevation in basal pressure above baseline duodenal pressure during phase III. Basal pyloric pressure varied between subjects in phases I and II, being elevated in some but not in others. Subjects restudied on a separate day often showed a different pattern of activity. Pyloric pressure increased gradually in response to duodenal acidification. This response was blocked by pretreatment with naloxone. The pylorus also showed phasic activity, which was maximal in phase III. This phasic activity could not be distinguished from that of the adjacent antrum and duodenum. In conclusion, pyloric pressure patterns showed marked variation within and between subjects. These variations may explain some of the differences between previous studies.

Continuous recording of pyloric sphincter pressure in dogs. Relationship to migratory motor complex.

Antral, pyloric, and small bowel intraluminal pressures were continuously recorded in dogs with gastric and duodenal cannulae. A cyclic phasic activity related to fasting motility in the antrum and small bowel was observed at the level of the pylorus. During phase I of the interdigestive motility complex, manometry was characterized by pressure variations of 31 +/- 2 cm H2O. During phase II, two type of waves were observed: small waves similar to those seen during phase I, with superimposed waves of higher amplitude (89 +/- 1.9 cm H2O). Pyloric pressure during phase III, showed a predominance of waves of even greater amplitude: 103 +/- 3.9 cm H2O. A basal tone of 65.6 +/- 3.2 cm H2O above the duodenal pressure was recorded throughout the period of study; but during phase III, frequent decreases in basal pressure were also observed. This relaxation of the pylorus during phase III of the IDMC may be related to the mechanism for size discrimination of particles leaving the stomach at the gastroduodenal junction.

Effects of aspirin and prostaglandin E2 on interdigestive motility complex and duodenogastric reflux in man.

Both increased duodenogastric reflux and chronic aspirin ingestion are associated with the development of gastric ulcers in man. Animal studies suggest aspirin increases duodenogastric reflux. Prostaglandin E2 protects gastric mucosa from the effects of many injurious agents and inhibits gastric motility, but its effect on duodenogastric reflux is unknown. We have studied the effects of aspirin and a synthetic derivative of prostaglandin E2 on duodenogastric reflux during fasting in six normal subjects, while concomitantly monitoring gastrointestinal motility by means of a perfused catheter system. We found that duodenogastric reflux (as measured by bile salt output in gastric aspirates) increased significantly (P less than 0.05) following both the prostaglandin E2 derivative and aspirin. This increase occurred in phases II and III of the interdigestive motility complex. Both drugs were associated with a significant reduction (P less than 0.05) in frequency and amplitude of antral contraction during phase II. Both drugs also induced a significant disruption (P less than 0.01) of phase III, increasing the number of complexes without an antral and duodenal component. These effects of aspirin may be one of the factors predisposing to the gastric mucosal damage associated with aspirin. The prostaglandin E2 derivative protects gastric mucosa by mechanisms other than reducing duodenogastric reflux and ameliorating the motility disturbances caused by aspirin.

Abnormalities of interdigestive motility complex and increased duodenogastric reflux in gastric ulcer patients.

Just as cyclic changes in motility and secretions occur during fasting, recent evidence demonstrates that duodenogastric reflux during fasting is also cyclic and related to the motility and secretory variations. We investigated the characteristics of the migrating motility complex and duodenogastric reflux in 17 patients with gastric ulcer and compared these characteristics to those of 16 healthy subjects. We found three abnormalities of the complex in patients with gastric ulcer: (1) the antral motility was significantly decreased during the phase II of the complex (P less than 0.05) when compared to controls; (2) in about two thirds of them, the phase III of the complex was initiated at the duodenum or more distally; and (3) the mean bile salt concentration in the gastric aspirate was significantly higher (P less than 0.05) than that of the controls. We observed no relationship between the ulcer activity, the location of the crater, and the motility or reflux abnormalities.

Distinctive patterns of interdigestive motility at the canine ileocolonic junction

Studies of interdigestive motor activity in the distal ileum, ileocolonic sphincter, and proximal colon were performed in two groups of dogs: (i) in those with ileocolonic loops that maintained neuromuscular continuity with the proximal intestine, we used an intraluminal side-hole assembly; (ii) in those with intact bowel, we attached extraluminal strain gauge transducers. Both groups of animals were equipped also with serosal electrodes. Positioning of motor sensors could be defined accurately by (a) a clear separation of rhythmic frequencies between those of the distal ileum (mean 10.8 cycles/min) and proximal colon (mean 6.2 cycles/min) and (b) the characteristic motor patterns of the ileocolonic sphincter. Analysis of motor activity in the segment demonstrated four distinct patterns: (i) irregular, apparently random phasic waves, (ii) rhythmic bursts of contractions corresponding to phase III of the migrating motor complex, (iii) other slowly propagated bursts of rhythmic activity (mean duration 3.6 min) recurring on average every 10 min, and (iv) single, prolonged (mean duration 16.7 s), high amplitude (mean 271 cmH2O) waves that propagated rapidly (“prolonged propagated contractions”). The latter two patterns appear unique to, or unusually prominent in, this region. A high degree of motor coordination between the distal ileum, ileocolonic sphincter, and proximal colon was also recognized. Thus, the patterns of motor activity suggest a specialized function for the distal 30 cm of ileum, the ileocolonic sphincter, and the proximal colon. These unique and coordinated patterns of motility deserve further exploration, especially in relation to ileocolonic transit and actions of the sphincter as a barrier to colo-ileal reflux.

Comparative effect of gastrin on hydrogen ion secretion, antroduodenal motility and the interdigestive motility complex (IDMC) in man

The physiological role of gastrin in H+ secretion is well established. We decided to study the effects of physiological doses of gastrin (as evidenced by H+ secretion and postprandial serum gastrin levels) on antroduodenal motility in order to delineate its role in antral motility regulation. Nine healthy male subjects, mean age 31 years, had two studies on different days. On day 1, gastroduodenal motility was monitored with a continuously perfused catheter system while gastric secretions were aspirated. After a basal period of 45 min, human synthetic gastrin (hG-17) was infused intravenously in consecutive doses of 6.25, 25, 100, and 400 pmol/kg/hr during 45 min each. On day 2, all subjects had a standard protein meal. Blood was withdrawn on both days for gastrin measurement by RIA. Increasing amounts of hG-17 caused a stepwise increase in serum gastrin and acid output. The D50 for H+ secretion was 25 pmol/kg/hr hG-17. The mean postprandial gastrin level was 31 +/- 5 pM, a level which was comparable to that seen during infusion of hG-17 6.25 pmol/kg/hr. At these serum gastrin levels, antral motility was either reduced or unchanged. Duodenal motility was unchanged. A reduction in the antroduodenal motility ratio was seen at these levels, but there was no interruption of the interdigestive motility complex. These results suggest that at physiological levels, gastrin by itself does not seem to have a major role in human antroduodenal motility regulation.

Canine interdigestive and postprandial gallbladder motility and emptying.

The objectives of this study were to characterize intraluminal gallbladder pressure during fasting and postprandially and to determine the relationships between its intraluminal pressure and emptying. Conscious dogs, with chronic indwelling gallbladder and duodenal catheters to measure pressures and infuse nonabsorbable markers, were used to quantify intraluminal pressures and emptying of gallbladder contents and bile into the duodenum during interdigestive and postprandial periods. During the interdigestive period, a brief rise in intragallbladder pressure followed by the flow of bile and 20% of gallbladder marker into the duodenum occurred only during phase II (a period of irregular duodenal contractility preceded by absent duodenal activity, phase I, and followed by a period of regular duodenal contractility, phase III). We suggest that intragallbladder pressure increased secondary to contraction of the gallbladder against a closed sphincter of Oddi and its decline to base line was accompanied by sphincter relaxation, partial gallbladder emptying, and flow of bile into the duodenum. Postprandially, intragallbladder pressure transiently increased and was followed by an isotonic phase lasting 74 +/- 12 min that ended with the onset of rhythmic large-amplitude pressure elevations that continued for 5.1 +/- 1.6 h. Gallbladder emptying was most rapid during the first 30 min postprandially and was completed by 2 h. Thereafter, large-amplitude gallbladder pressure elevations may prevent gallbladder filling and divert hepatic bile into the duodenum until return of the fasting pattern.

Interdigestive gastrointestinal motility and secretion of gastric acid and pancreatic enzymes in young cigarette smokers.

The basal (interdigestive) gastrointestinal motor activity and the interdigestive gastric acid and pancreatic amylase secretion were determined in 10 young smokers (mean age 23 years) and 7 nonsmokers (mean age 26 years). There was no significant difference in the length of the interdigestive motor complex between smokers and nonsmokers, but the speed of transmission of the activity front (phase III) in the upper intestine was significantly (p less than 0.05) greater in smokers than in nonsmokers. No significant overall changes in the interdigestive gastric acid and pancreatic amylase outputs were observed between the two groups studied.

Growth hormone releasing factors in the brain and the gut: Chemistry, actions, and localization

Within the physiological range of other known releasing factors, human pancreatic tumor growth hormone releasing factor (hpGRF) is specific for GH release. Data concerning hpGRF action on cAMP and GH are consistent with the concept of cAMP acting as a second messenger for this releasing factor. hpGRF-stimulated GH release is Ca ++ dependent. Exogenous hpGRF 40 does not alter the interdigestive gastric motility or secretion of gastrin and motilin in dogs, while large doses of hpGRF stimulate somatostatin release into the hepatic portal blood of the rat. Significant GRF activity as determined by a rat pituitary perifusion system is confined within the median eminence and the arcuate nucleus, though detectable but insignificant GRF activity is present in other area of the hypothalamus and cortex in the rat. GRF activity is present in the ovine brain as well as in the gut. Both tissues contain large (between 4000–5000 daltons) and small (but possibly larger than 1000 daltons) m.w. GRF materials. GRF appears to be structurally different between species and more than one GRF may be present within the same species. One of the ovine brain peptides with GH-releasing activity was partially characterized as His-Ser-Asp-Gly-Ile-Phe-Thr-Asp-Ser-Tyr-Lys-Arg-Try-Asn-Lys-Glu-Met-Ala-Lys—which is similar to rat GRF and porcine VIP having His at the N-terminus. Another peptide with GRF activity which eluted earlier on reverse phase HPLC and later on cation exchange chromatography has also been obtained in a pure form. In addition, VIP which has low but significant GRF activity in vitro may potentiate the GRF action of hpGRF in vivo and in vitro under certain conditions, suggesting a potentially physiologically important interplay of VIP and GRF with respect to GH secretion.

Abnormalities of interdigestive motility of the small intestine in patients with Chagas' disease

The fasting motor activity of the upper small intestine was studied in 36 patients with chronic Chagas' disease, which is known to be associated with extensive lesions of the myenteric plexuses, and the results compared with those obtained in 15 control subjects. The migrating motor complex (MMC) was detected as frequently in the Chagas' disease group as in the control group, and the frequency of contractions during the activity front was virtually the same in the two groups. In the Chagas' group the propagation of the activity fronts was slower, their duration was longer in the jejunum, but not in the duodenum, and the calculated length was shorter than normal. Chagas' disease patients without clinical manifestation or x-ray pathology of the digestive tract had no abnormalities of the MMC. These findings suggest that the intramural nervous system of the gut plays a role in the normal migration of the MMCs along the small intestine.

Motilin regulation of canine interdigestive intestinal motility.

The objective was to determine whether motilin regulates cyclical interdigestive motility in the jejunum as well as in the duodenum. In four conscious dogs with an intact innervated duodenum, an autotransplanted (extrinsically denervated) 75-cm loop of proximal jejunum, and an autotransplanted, in situ distal jejunum, interdigestive myoelectrical complexes cycled independently in all three regions of small bowel. Plasma concentration of motilin was greater during phase III of the duodenal cycles (304 +/- 37 pg/ml) than during phase I (235 +/- 37 pg/ml) or phase II (235 +/- 39 pg/ml; P less than 0.05), but the concentration did not vary consistently with the phases of the cycles in the autotransplanted jejunal segments. Intravenous infusions of motilin (0.6 microgram/kg/min for 5 hr), begun 15-30 min after passage of phase III through the duodenum, shortened the interval between phase IIIs in the duodenum from 147 +/- 14 min before infusions to 44 +/- 3 min during the infusions (P less than 0.05), but did not alter consistently the interval between phase IIIs in the autotransplanted jejunal segments. Feeding decreased plasma motilin concentration. The data were consistent with motilin regulation of interdigestive motility in intact, innervated canine duodenum but not in extrinsically denervated jejunum.

Effects of neurotensin on small bowel propulsion in intact and vagotomized rats.

The effects of intravenous infusion of neurotensin on small bowel motility was studied in conscious rats. During 1 h a standardized test meal of glucose, polyethyleneglycol (PEG) 3000, phenol red and 125I-labelled polyvinylpyrrolidone was administered via a permanent gastric catheter and simultaneously the bile-excreted radio-pharmaceutic 99Tcm-Solco-HIDA was infused intravenously. Immediately after the infusions the gastrointestinal specimen was excised and examined for distribution of radioactivity. Both doses of neurotensin (0.1 and 0.3 microgram . kg-1 . h-1) resulted in an increase in the neurotensin-like immunoreactivity (NTLI) of plasma to levels similar to that found after a fatty meal. Concurrently the small bowel transport pattern was changed from an interdigestive state to one similar to that found after a meal. In animals not receiving the gastric test meal, neurotensin (0.1-0.5 microgram . kg-1 . h-) had no effect on motility. Infusion of the gastric test meal alone did not change the interdigestive motility or the NTLI value. This indicates that the presence of gastric infusates potentiates the effect of neurotensin on small bowel motility. The motility response to neurotensin did not differ between intact and vagotomized animals. This contrasts to earlier findings that the small bowel motility response to a fatty meal is dependent on intact vagal function. Thus, a difference in the mechanism responsible for the motility responses between a fatty meal and neurotensin exists. In view of this finding it seems reasonable to assume that neurotensin cannot be the only factor responsible for the shift in motility found after a fatty meal.

Evidence for cholinergic and vagal noncholinergic mechanisms modulating plasma motilin-like immunoreactivity.

Basal concentrations of plasma motilin-like immunoreactivity (MLI) and responses to insulin-induced hypoglycemia were measured in healthy subjects (n = 13) in diabetics with clinical evidence of autonomic neuropathy (AN; n = 7), in diabetics without AN (n = 9), and in five recently (6--12 months) vagotomized subjects. Mean basal MLI concentrations were similar in the healthy subjects (141 +/- 21.5 pg/ml) and diabetics without AN (124 +/- 22.4 pg/ml), but were significantly higher in diabetics with AN (349 +/- 71.5 pg/ml) and in vagotomized subjects (381 +/- 47.6 pg/ml). In both healthy subjects and diabetics without AN, the acute administration of insulin (0.1--0.2 U/kg) caused a fall in the mean MLI concentration, reaching a nadir within 20 min, returning to the basal concentration by 60 min, and rising above basal levels by 90 min. In diabetics with AN and vagotomized subjects, the fall in MLI persisted for 90 min. Intravenous atropine administered 15 min after the insulin injection in healthy subjects did not impair the return to basal. The responses were not related to the degree of hypoglycemia, the absolute or relative fall in blood glucose concentrations, or differences in blood glucose among healthy subjects, diabetics, or vagotomized subjects. It appears, therefore, that insulin lowers plasma MLI levels, which are restored to basal by a vagal noncholinergic mechanism. Furthermore, the vagus exerts a suppressive effect on basal MLI levels, and vagotomy and diabetic autovagotomy are associated with abnormal elevation of MLI levels. Since motilin is thought to be important in interdigestive intestinal motility, abnormalities in MLI secretion in diabetics with autonomic neuropathy may contribute to gastrointestinal stasis and erratic diabetic control.

Solid-phase synthesis and biological activities of gastrointestinal hormones: Secretin and motilin

Many successful solid-phase syntheses of peptide chains in the region of 20–40 amino acid residues have now been routinely reported. Utilizing standard solid-phase synthetic methodologies but, particularly, new and powerful purification techniques we have been developing rapid and efficient preparative routes for the numerous neuro-gastrointestinal peptides. In the present study, secretin and motilin were obtained in 16% and 10% yields, respectively, after simplified two-step purification of hydrogen fluoride-cleaved peptides by gel filtration followed by preparative high performance liquid chromatography. Peptides were essentially homogeneous by TLC and analytical high performance liquid chromatography. Secretin was found to have full biological activity when tested against a standard sample of natural material for effects on pancreatic secretion in the dog. Motilin exhibited full biological activity on interdigestive motility in the dog. Secretin has been reported to undergo rearrangement with loss of bioactivity during purification and prolonged storage. We observed no obvious problems during our abbreviated purification schedule and have found no loss of purity of peptide which has been kept for 6 months as powder lyophilized from dilute acetic acid.

Sham feeding disrupts the interdigestive motility complex in man.

We have examined the effect of sham feeding on the interdigestive motility complex (IDMC) and the release of pancreatic polypeptide (PP) in a group of normal volunteers. The duration of the intervals in phase III of the IDMC was significantly delayed (p less than 0.01) after sham feeding, whereas there was an increase in plasma PP levels in all subjects. These results support the presence of an inhibitory vagal mechanism for the distal stomach and intestinal motility.