Interdigestive Gastroduodenal Motility Research Articles

Effect of Glucagon, Glicentin, Glucagon-like Peptide-1 and-2 on Interdigestive Gastroduodenal Motility in Dogs with a Vagally Denervated Gastric Pouch

Background: We previously reported that inhibition of gastric motility and hypertrophy of the small intestinal mucosa were observed after ileo-jejunal transposition which induced hypersecretion of enteroglucagon. Our aim was to study the effect of four enteroglucagon-related peptides (glucagon, glucagon-like peptide (GLP)-1, -2 and glicentin) on gastroduodenal motility and their mechanisms of action. Methods: The effect of these four peptides on motilin-induced interdigestive contractions was studied in dogs with vagally denervated gastric pouches equipped with four strain gauge force transducers on the pouch, gastric body, antrum and duodenum. Whether or not nitric oxide synthase inhibitor or phentolamine and propranolol reverses the inhibitory effect of those peptides was also studied. Results: Glucagon inhibited contractions in the pouch and stomach but had no effect on duodenal contractility. GLP-1 inhibited contractions at all sites. GLP-2 inhibited contractions in the pouch but did not affect motility in the neurally intact gastroduodenum. Glicentin had no effect on contractions at any site. Pretreatment with either a nitric oxide synthase inhibitor or phentolamine and propranolol reversed the inhibitory effect of glucagon, GLP-1 and GLP-2 on contractions in the pouch, but did not alter the inhibitory effect of glucagon and GLP-1 on motility in the neurally intact stomach and duodenum. Conclusions: These results suggest that the effects of four peptides on gastroduodenal motility differ, and changes occur in the enteric neural modulation of motor activity after chronic surgical extrinsic denervation.

Dose-Related Stimulatory Effect of Clarithromycin on Interdigestive Gastroduodenal Motility

Background/Aims: The effect on interdigestive gastroduodenal motility of different doses of clarithromycin, an antibiotic commonly used for Helicobacter pylori eradication, has been investigated. Methods: Gastroduodenal motility was recorded by means of a low-compliance manometric system in 15 healthy subjects. Thirty minutes after the first phase III of the migrating motor complex, clarithromycin (CLA) was infused intravenously at a dose of 100 mg in 5, 250 mg in 5 and 400 mg in 5 subjects, randomly and in a double-blind manner, continuing the recording for at least 1 h. A further study was carried out on 10 subjects, 5 of whom received 50 mg CLA and 5 normal saline with the same modalities. Results: After 100 mg CLA a premature gastroduodenal phase III ensued in all cases, which showed a duration, propagation velocity and wave frequency not significantly different from the spontaneous one and was followed by a clear phase I. A premature gastroduodenal phase-III-like activity occurred in 3 cases of 250 mg CLA and 2 cases after 400 mg CLA, followed by a very short or absent phase I and characterized by a long duration of the antral phase III, while in the remaining cases a long-lasting sequence of about 1/min of antral waves propagated to the duodenum appeared, sometimes preceded by an antral phase-III-like activity not propagated to the duodenum. After 50 mg CLA a premature phase III appeared in 2 cases, while a not premature phase III appeared in 2 cases after saline. Conclusion: CLA shows a dose-related stimulatory effect on interdigestive gastroduodenal motility varying from the initiation of a typical phase III to a prolonged sequence of gastroduodenal coordinated waves. These motor effects of CLA suggest potential therapeutic applications.

In Dyspeptic Patients without Gastric Phase III of the Migrating Motor Complex, Helicobacter pylori Eradication Produces no Short-term Changes in Interdigestive Motility Pattern

Background: The relationship between Helicobacter pylori infection and interdigestive gastroduodenal motility in functional dyspepsia is still uncertain. Recent data from a large series documented that in dyspeptic patients without gastric phase III of the interdigestive migrating motor complex (MMC), the prevalence of bacterial infection was significantly higher. Since most H. pylori-positive dyspeptic patients have coexisting chronic gastritis, whether or not dyspepsia per se rather than bacterial colonization or chronic inflammation of the gastric mucosa may account for the observed interdigestive motility pattern is unknown. Our aim was to compare the interdigestive gastroduodenal motility pattern and dyspeptic symptoms before and 1 month after bacterial eradication in 20 H. pylori-positive dyspeptic subjects with chronic non-atrophic gastritis and without gastric phase III of the MMC, who were randomly allocated to receive eradication treatment (n = 10) or not (n = 10). Methods: Upper GI endoscopy with duplicate biopsies in antrum and corpus, 240-min interdigestive gastroduodenal manometric recording and symptoms assessment were performed before and 1 month after the treatments; bacterial eradication was confirmed by 13C-urea breath test. Results: After H. pylori eradication, neither in the incidence of antral and duodenal phase III of MMC nor in the phase II motility index values were any changes observed. Symptomatic improvement was recorded in both groups, with no significant differences between eradicated patients and controls. Conclusions: In dyspeptic patients with chronic non-atrophic gastritis and without gastric phase III of MMC, H. pylori eradication influences neither the interdigestive motility pattern nor the symptoms in the short-term period.

Human duodenogastric reflux, retroperistalsis, and MMC.

The aim of this study was to determine to what extent human migrating motor complex (MMC)-related secretory phenomena are influenced by a recently discovered period of duodenal retroperistalsis during late phase III. A constant-flow perfusion technique was used to measure gastric appearance of acid, bicarbonate, pepsin, bilirubin, IgA, and duodenally infused [14C]polyethylene glycol (PEG) 4000 in 12 healthy volunteers. Interdigestive gastroduodenal motility was recorded by digital manometry. During late antral phase II and III, the gastric lumen was acidified (P < 0.005 phase III vs. phase I) together with a marked increase in luminal pepsin output (3.1 +/- 1.2 during phase III vs. 0.25 +/- 0.08 kU/5 min in phase I, P < 0.01), followed by a realkalinization due to a simultaneous reduction of acid secretion and a duodenogastric reflux, aided by retrograde peristalsis, of bicarbonate and IgA but not of bilirubin, at the end of antral phase III (P < 0.05 phase III vs. phase I values). This physiological duodenoantral reflux phenomenon may play an important role in the chemical and immunological restitution of the antral mucosal barrier function after the exposure to high acid and pepsin concentrations during antral phase III activity.

Gastric acid inhibits antral phase III activity in duodenal ulcer patients.

Fourteen patients with duodenal ulcers and eight healthy volunteers were examined to measure interdigestive gastroduodenal motility and plasma motilin. In order to study the effects of gastric acid on the gastroduodenal motility, 20 mg of famotidine was administered intravenously. The motility index of the gastric antrum and the duodenum, as well as the pH in the duodenal bulb were calculated. The duodenal pH was significantly lower and the gastric motility index was significantly weaker before the duodenal interdigestive migrating complex (IMC) in the ulcer patients than in the controls. Motilin levels increased before the duodenal IMC and decreased afterwards in both groups. Famotidine significantly increased the duodenal pH and the gastric motility index before the IMC, but no changes in the motilin level were noted. We conclude that duodenal ulcer patients have duodenal hyperacidity that results from increased inflow from the antrum and antral hypomotility during the gastric IMC and that these changes are normalized by the administration of famotidine. These results suggest that gastric acid inhibits antral contraction during the gastric IMC.

The Inhibitory Effect of Octreotide on Exocrine Pancreatic Secretion in Conscious Dogs

The effects of somatostatin and its analogue, octreotide (SMS201-995), on pancreatic secretion and gastroduodenal motility in response to secretin and cholecystokinin octapeptide (CCK-8) were studied in five conscious dogs. Intravenous infusions of octreotide or somatostatin (1 nmol kg-1 h-1) inhibited periodic pancreatic secretion and the potentiation of fluid and bicarbonate responses to secretin at 60 ng kg-1 h-1 associated with the interdigestive gastroduodenal motility peaks (migrating motor complex). Pancreatic fluid and bicarbonate responses to secretin (125-1,000 ng kg-1 h-1) were not inhibited by octreotide or somatostatin. Pancreatic protein and enzyme responses to secretin and CCK-8 at 50 and 100, but not at 200 and 400, ng kg-1 h-1 were inhibited by octreotide and somatostatin. These inhibitory effects were similar to those of atropine (25 micrograms kg-1 h-1). The inhibition of protein responses to CCK-8 (100 ng kg-1 h-1) was dependent on octreotide dose. It is concluded that both octreotide and somatostatin, like atropine, inhibit interdigestive pancreatic secretion and the responses to small, but not large, doses of secretin and CCK-8 in conscious dogs.

Interdigestive gastroduodenal motility and cycling of putative regulatory hormones in severe obesity.

The aim of the present study was to evaluate interdigestive gastrointestinal motility and its coordination with plasma concentrations of motilin and pancreatic polypeptide (PP) in 14 patients with severe obesity and in 10 control subjects with normal body weight. Motor activity of the stomach, duodenum, and proximal jejunum was recorded by using an eight-lumen catheter. Blood samples were drawn for determination of interdigestive motilin and PP plasma concentrations. We observed no difference in total duration of the migrating motor complex (MMC) or of phases I, II, or III of the MMC. Gastric phase-III activity occurred less frequently in severely obese patients (only 15% originating in the stomach) than in controls (65%; p less than 0.01). Plasma motilin concentrations were decreased in obese patients in phase I (127 +/- 17 pg/ml in controls versus 87 +/- 10 pg/ml in obese), in phase II (189 +/- 26 pg/ml controls versus 134 +/- 15 obese) and in phase III (195 +/- 29 pg/ml controls versus 153 +/- 28 pg/ml obese). Peak motilin release occurred in synchrony with phase-III activity and was greater in controls than in obese patients. Plasma PP concentrations did not differ from those of controls during any phase of the MMC. These results further suggest a potential role for motilin in regulating gastrointestinal motor activity and indicate a potential defect in this regulatory mechanism in severe obesity. Whether the relationship between disordered motor activity and motilin release is etiologic with regard to the pathophysiology of obesity remains to be determined.

Interdigestive Gastroduodenal Motility in Patients with Active and Inactive Duodenal Ulcer Disease

The interdigestive gastroduodenal motility was studied by means of a manometric probe in 6 patients with active duodenal ulcer and acid hypersecretion, in 6 patients with ulcer disease in remission (inactive) and normosecretion and in 8 healthy subjects with normosecretion. After a basal recording period sufficient to record at least two activity fronts of the migrating motor complex (MMC), an intraluminal infusion of isotonic NaHCO3 was carried out for 180 min in patients with active duodenal ulcer, whereas in patients with ulcer in remission an HCl solution was infused for 180 min. Patients with active duodenal ulcer showed a basal motility with a longer than normal MMC cycle and a shorter than normal activity front, while patients with ulcer in remission showed a cyclic motor activity not significantly different from that of normal subjects. The NaHCO3 infusion in patients with active ulcer restored a near-normal motility, whereas the HCl infusion in patients with ulcer in remission induced a motility similar to that of patients with active ulcer. These data indicate that the increase in gastric acid secretion is responsible for the decrease in frequency and duration of MMC activity fronts, which have the function of cyclically clearing the gastroduodenal lumen. Consequently, acid and bacteria may remain a longer than normal time in contact with the gastroduodenal mucosa, which, in this manner, may be greatly exposed to the risk of peptic lesions.

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.