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PubMed2004

The role of endogenous opioids in the control of gastrointestinal motility: predictions from in vitro modelling.

Gastrointestinal motility can be assessed in vitro by investigating the effects of drugs or gene knockouts on intestinal propulsion, and on neurone-mediated responses evoked by electrical field stimulation (EFS). The latter predominantly measure enteric motor activity and can detect prokinetic activity of exogenous agents. Some evidence suggests that naloxone has prokinetic activity when evaluated for an ability to modulate responses to EFS, but the effects are inconsistent across different species or intestinal regions. Models of intestinal peristalsis measure an integrated sensory-motor nerve function and possess more intact neuro-neuronal connections. In such preparations, the effects of naloxone also suggest a prokinetic property but again, this is inconsistent. By contrast, consistent prokinetic activity of naloxone is apparent in models where peristalsis is compromised by drug-induced suppression of motor nerve activity or by modulation of endogenous processes using receptor antagonists or inappropriate intraluminal distension. These data suggest that endogenous opioids play little or no role in normal intestinal physiology, but suppress intestinal motility when motor function is compromised. Consequently, drugs that antagonize opioid receptors may exert prokinetic activity in conditions where intestinal motility is reduced, such as constipation. Further work is required to elucidate the opiate receptor(s) involved.

Animals↗
PubMed1995

Role of nuclear medicine in evaluating patients with suspected gastrointestinal motility disorders.

Functional symptoms caused by gastrointestinal motility disorders are relatively common in the general population. Knowledge of the relationship between symptoms and the underlying gastrointestinal dysmotility provides physicians with a framework for successful evaluation and treatment of patients with possible motor disorders of the gastrointestinal tract. Scintigraphy provides for noninvasive and quantitative assessment of physiological transit throughout the gastrointestinal tract, and it is extremely useful for diagnosing gastrointestinal motor dysfunction. The wide range of scintigraphic studies now available supplement other diagnostic tests for evaluation of all segments of the gastrointestinal tract.

Colon↗
PubMed1999

Short-chain fatty acids present in the ileum inhibit fasting gastrointestinal motility in conscious pigs.

Colonic compounds, primarily short-chain fatty acids (SCFAs), inhibit gastric tone in humans. However, since colonic compounds reflux into the ileum, SCFAs might act also at the ileal level. This study evaluates the effects of the contact of SCFAs with the ileum alone towards gastrointestinal motility in fasted conscious pigs. Gastrointestinal motility was recorded during ileal infusion of a mixture containing acetate, propionate and butyrate in intact vs ileostomized animals (n = 10). Ileal infusions of isomolar (500 mmol L-1) vs isocaloric (600 kJ L-1) SCFAs were also performed. SCFA mixture reduced significantly the amplitude and increased the frequency of antral contractions in intact (motility index: 2624 +/- 503.4 vs 4077 +/- 388.2) and ileostomized pigs (motility index: 2428 +/- 678.1 vs 4709 +/- 773.4) compared with iso-osmotic saline. SCFAs at isomolar concentrations inhibited equally gastric motor pattern irrespective of their chemical structure. On the contrary, isocaloric concentrations of SCFAs induced graded effects: acetic acid being the most potent to reduce gastric motility. In conclusion, SCFAs inhibit gastrointestinal motility by a direct contact with the ileum. This inhibition was concentration dependent.

Animals↗
PubMed2001

Ontogeny of fetal rabbit upper gastrointestinal motility.

BACKGROUND: The gastrointestinal (GI) tract performs the digestion, propulsion, and absorption of nutrients both pre- and postnatally, although little is known about the development of fetal motility. We evaluated the development of GI motility using a novel fetal rabbit model. METHODS: Nine pregnant rabbits were obtained and three litters were studied at day 24 (n = 24), 27 (n = 29), and 30 (n = 24) of their 31-day gestation. Under ultrasound guidance fetal position was identified, a spinal needle was percutaneously inserted into each fetal stomach, and fluorescein, labeled with color-coded microspheres, was injected. Two hours later, fetuses were delivered and weighed, and the small intestine was harvested. The absolute length of fluorescein traveled was measured by ultraviolet light optical density and the percentage motility was calculated by dividing the absolute length of fluorescein traveled by the total small intestinal length. RESULTS: All injected fetuses survived. The length of fluorescein traveled significantly increased from day 24 (8.1 +/- 2.1 cm) to day 27 (18.8 +/- 4.6 cm) and 30 (22.6 +/- 5.2 cm). The length of fluorescein traveled significantly correlated with body weight on day 27 and 30. Calculated percentage motility significantly increased from day 24 to 30. However, percentage motility showed no correlation with fetal weight. CONCLUSIONS: This study describes a novel rabbit model for the assessment of in vivo fetal GI motility. Motility matured during the last third of gestation when assessed by the absolute length of fluorescein travel and the percentage motility. These results confirm that late-gestation fetuses have developed sufficient motility to propel potential nutrients, drugs, or gene therapy vectors to the small intestinal absorptive surface area.

Animals↗
PubMed1987

Total duodenectomy: effect on canine gastrointestinal motility.

Motor activity of the upper gastrointestinal tract undergoes a cyclic pattern during fasting called the migrating motor complex (MMC). The role of the duodenum in controlling this cyclic activity was studied in the dog. Five dogs served as controls. In four other dogs, the entire duodenum and the proximal 20 cm of jejunum were resected. The ostia of the bile duct and pancreatic duct were preserved as "mucosal buttons" and reimplanted in situ into the jejunum after gastrojejunostomy. All dogs had manometry catheters placed into the stomach and serosal electrodes implanted onto the small intestine to monitor gastrointestinal motility. All control dogs showed the characteristic MMC in the stomach and small intestine, the period being 112 +/- 16 min (mean +/- SEM). After total duodenectomy, an irregular, noncyclic pattern of contractions occurred in the stomach in two of the four dogs during fasting. The other two dogs had a cyclic pattern of gastric motility; however, the overall characteristics of these cyclic patterns of gastric motility differed from that of controls. A variable proportion of the phases of cyclic gastric activity did not fit the criterion for temporal coordination with the jejunum as defined from study of control dogs. In contrast, jejunal motility in all four dogs after total duodenectomy continued to exhibit the characteristic MMC, but the period of the cycle (58 +/- 7 min) was shorter than in controls (P less than 0.05). "Ectopic" jejunal activity fronts with no preceding gastric contractions were frequent. After total duodenectomy, plasma concentration of motilin remained lower than normal and showed no cyclic variation with the jejunal MMC. After total duodenectomy, feeding interrupted the fasting motor pattern of the stomach as in controls, but did not disrupt the MMC in the jejunum. We concluded that the duodenum has an important role in initiating cyclic gastric motor activity and in coordinating motor activity between the stomach and the small intestine.

Animals↗
PubMed1992

Effects of macrolide antibiotics on gastrointestinal motility in fasting and digestive states.

The effect of macrolide antibiotics on gastrointestinal motility was studied in unanaesthetized dogs by using strain-gauge transducers. Midecamycin acetate, leucomycin, josamycin and acetylspiramycin, which are 16-membered macrolides, did not affect the gastrointestinal motility and no symptoms of gastrointestinal disorder were observed. On the other hand, erythromycin, roxithromycin, clarithromycin and oleandomycin, which are 14-membered macrolides, caused giant contraction and disorder symptoms. Moreover, it was found that the glycosidic linkages of the lactone ring were necessary for a structure to exert strong contractile activity.

Animals↗
PubMedDate not supplied

Effect of atropine on gastrointestinal motility and the bioavailability of cyclosporine A in rats.

The effect of atropine on gastrointestinal motility and the bioavailability of cyclosporine A (CyA) was studied in rats. Atropine dose-dependently inhibited gastrointestinal motility, and the ID20 and ID50 doses of atropine were chosen to study the bioavailability of CyA. After oral administration of CyA, the bioavailability was about 27%, and with increasing doses of atropine the area under the concentration-time curve and the peak blood concentration of CyA decreased. Atropine had no significant effect on the time of peak blood concentration (Tmax) and the mean residence time. These data suggested that there was prehepatic metabolism of CyA; thus a luminal perfusion study was performed. When CyA was perfused through rat stomachs by a recirculation method, the content of CyA in the perfusate rapidly decreased. However, the tissue content of CyA was not very high. These results indicate that changes in gastrointestinal transit as well as gastrointestinal metabolism of CyA may be important causes of the wide variability of its absorption in humans.

Administration, Oral↗
PubMed1995

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↗
PubMed1989

Effect of duodenectomy on interdigestive pancreatic secretion, gastrointestinal motility, and hormones in dogs.

We tested the hypothesis that the duodenum is necessary to coordinate interdigestive pancreatic trypsin secretion with gastrointestinal motility and determined whether duodenectomy altered interdigestive cycles of plasma motilin and pancreatic polypeptide and their relationship to trypsin secretion and motility. Consequently, in normal and duodenectomized dogs, we measured trypsin secretion, gastrointestinal motility, and plasma concentrations of motilin and pancreatic polypeptide during the interdigestive period. After duodenectomy, peaks of trypsin secretion continued to cycle at normal intervals (102 +/- 15 min), but the amounts of trypsin were reduced during peaks of secretion (P = 0.02) and throughout the entire cycle (P = 0.02). Trypsin secretory cycles after duodenectomy, however, were not coordinated with cycles of interdigestive motility, and the plasma concentrations of motilin (P = 0.02) and pancreatic polypeptide (P = 0.05) were reduced and had no cyclic pattern. In addition, we confirmed that duodenectomy alters canine interdigestive antral motility, interrupts coordination between antral and intestinal motility, and shortens the period of jejunal migrating motor complexes. We conclude that duodenectomy disrupts the relationship between the cycles of interdigestive gastrointestinal motility and trypsin secretion and reduces the amount of interdigestive trypsin secretion. These effects of duodenectomy may be due to interruption of the duodenopancreatic neural connections or the hormonal abnormalities we have described. The loss of the cyclic pattern of plasma pancreatic polypeptide after duodenectomy suggests that the duodenum controls the release of pancreatic polypeptide by either a neural or hormonal mechanism.

Animals↗
PubMedDate not supplied

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 micrograms/kg) but not after IV administration of 10 times higher doses. These results suggest that in dog CRF may be involved in the central control of the interdigestive gastric motility, these effects were not probably due to the release of ACTH and cortisol 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.

Adrenocorticotropic Hormone↗
PubMed2004

Autonomic neuropathy and gastrointestinal motility disorders in children and adolescents with type 1 diabetes mellitus.

INTRODUCTION: There is little information on the gastrointestinal motility abnormalities and autonomic neuropathy of children with gastrointestinal symptoms and type 1 diabetes mellitus (T1DM). METHODS: The authors studied 33 consecutive patients (mean age, 15.3 years; 13 males) with T1DM (median duration, 7.7 years) attending the outpatient clinic because of chronic dyspepsia (CD; n = 14), or chronic constipation (CC; n = 19), and 48 consecutive non-T1DM patients (mean age, 13.7 years; 18 males), who presented with similar symptoms (18 with CD; 30 with CC). Fasting serum motilin concentrations and cardiovascular autonomic function tests (CAFT) were assessed and compared with those of age- and gender-matched healthy control subjects. Gastric emptying half time (GE t1/2) of a solid meal and mouth-to-anus transit time (MATT) were measured in patients with CD and CC, respectively. RESULTS: CAFT was comparable between patients with T1DM and healthy control subjects. GE t1/2 and MATT were not different between T1DM patients and non-T1DM patients with CD and CC, respectively. However, a marginally significant positive correlation was found in the patients with T1DM between GE t1/2 and blood glucose concentrations (R = 0.54; P = 0.08). In addition, serum motilin concentrations were significantly lower in patients with T1DM compared with healthy control subjects (P < 0.0005), and in patients with T1DM and higher serum glucose concentrations compared with those with lower serum glucose concentrations (P = 0.03). CONCLUSION: Autonomic neuropathy is not an etiological factor of gastrointestinal symptoms in children and adolescents with diabetes. Mild or moderate hyperglycemia does not affect gastrointestinal motility.

Adolescent↗
PubMed1996

Gastrointestinal motility disorders.

A careful history can localize gastrointestinal motility disorders and suggest appropriate diagnostic tests. Dysphagia, odynophagia, heartburn and reflux have esophageal origins. The same symptoms occur in achalasia, a classic motor disorder of the lower esophageal sphincter, which can be diagnosed by barium swallow, endoscopy and esophageal motility studies. Nausea, vomiting, anorexia, bloating and abdominal pain are symptoms of motor disorders of the stomach and small intestine. When these symptoms are accompanied by unexplained right upper quadrant pain, elevated liver enzyme levels and unexplained recurrent pancreatitis, the diagnosis of impaired biliary motility is suggested. Colorectal motility disorders may present as abdominal pain, diarrhea, constipation and/or fecal incontinence. If symptoms do not resolve with dietary changes and appropriate medications and the anatomy is normal on lower gastrointestinal studies, colorectal motility studies may be indicated.

Biliary Dyskinesia↗
PubMed2004

Isolation of stimulants of gastrointestinal motility in beer.

BACKGROUND: Among various alcoholic beverages, it has reported that beer has a potent activity to stimulate gastric emptying. Our previous studies showed that beer congener stimulated gastrointestinal motility by directly stimulating muscarinic M3 receptor, present in smooth muscles of the gastrointestinal tract. However, active components that account for the action have yet to be identified. We attempted to isolate the stimulant(s) of gastrointestinal motility in beer. METHODS: Beer congener was prepared from beer and used to separate and purify active components by a series of liquid chromatography using affinity to muscarinic M3 receptor as an index. Gastrointestinal motility-stimulating activity was evaluated using a test for activity that causes contraction of longitudinal muscles in guinea pig ileum and a test for gastric emptying activity in mice. RESULTS: The active components (compounds A and B) were purified and isolated from beer by four liquid chromatography steps. The IC50 values of two active isolates to muscarinic M3 receptor were 0.65 x 10 g/ml and 2.30 x 10 g/ml, respectively. The concentrations of compounds A and B contained in beer were sufficient to explain most of the muscarinic M3 receptor binding activity of beer. The active fraction that contained both compounds A and B (which was 10 times as active as beer congener in muscarinic M3 receptor binding activity) dose-dependently contracted the longitudinal muscles of guinea pig ileum with an activity that was 20 times as potent as that of beer congener. The same active fraction significantly stimulated gastric emptying in mice with an activity 20 times as potent as that of beer congener. CONCLUSIONS: Two active components (compounds A and B) were isolated as gastrointestinal motility stimulants (muscarinic M3 agonists) in beer. These results suggest that the two isolated active components are the active entities of the gastrointestinal motility-stimulating effect of beer.

Animals↗
PubMed2002

Effect of L-NAME on nitric oxide and gastrointestinal motility alterations in cirrhotic rats.

AIM: To investigate the effect of L-NAME on nitric oxide and gastrointestinal motility alterations in cirrhotic rats. METHODS: Rats with cirrhosis induced by carbon tetrachloride were randomly divided into two groups, one n =13 receiving 0.5mg.kg(-1) per day of N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, for 10 days, whereas the other group (n =13) and control (n =10) rats were administrated the same volume of 9g.L(-1) saline. Half gastric emptying time and 2h residual rate were measured by SPECT, using (99m)Tc-DTPA-labeled barium sulfate as test meal. Gastrointestinal transition time was recorded simultaneously. Serum concentration of nitric oxide (NO) was determined by the kinetic cadmium reduction and colorimetric methods. Immunohistochemical SABC method was used to observe the expression and distribution of three types of nitric oxide synthase (NOS) isoforms in the rat gastrointestinal tract. Western blot was used to detect expression of gastrointestinal NOS isoforms. RESULTS: Half gastric emptying time and trans-gastrointestinal time were significantly prolonged(124.0 +/- 26.4 min; 33.7 +/- 8.9 min; 72.1 +/- 15.3 min; P<0.01), (12.4 +/- 0.5h; 9.5 +/- 0.3h; 8.2 +/- 0.8h; P<0.01), 2h residual rate was raised in cirrhotic rats than in controls and cirrhotic rats treated with L-NAME (54.9 +/- 7.6%,13.7 +/- 3.2%, 34.9 +/- 10.3%, P<0.01). Serum concentration of NO was significantly increased in cirrhotic rats than in the other groups (8.20 +/- 2.48) micromol.L(-1), (5.94 +/-1.07) micromol.L(-1) and control (5.66 +/- 1.60 micromol.L(-1), P<0.01. NOS staining intensities which were mainly located in the gastrointestinal tissues were markedly lower in cirrhotic rats than in the controls and cirrhotic rats after treated with L-NAME. CONCLUSION: Gastrointestinal motility was remarkably inhibited in cirrhotic rats, which could be alleviated by L-NAME. Nitric oxide may play an important role in the inhibition of gastrointestinal motility in cirrhotic rats.

Animals↗
PubMed1996

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↗
PubMed1994

Influence of urethane anesthesia and abdominal surgery on gastrointestinal motility in rats.

The influence of various experimental treatments on propulsive gastrointestinal motility was examined in rats, using inulin as a marker. In unanesthetized rats without any surgery, the distribution center of inulin, which was expressed as a dimensionless distance normalized by the length of the small intestine, reached 0.587 down the intestinal tract from the pylorus 60 min after the intragastric administration of inulin. However, the distribution center of inulin moved only 0.061 in 60 min in unanesthetized rats with minimial abdominal surgery for intraduodenal administration of inulin, and did not move in unanesthetized rats with cannulas for perfusion or in the rats anesthetized with urethane and treated with abdominal surgery. In urethane-anesthetized rats without surgery, almost 100% of the inulin was recovered from the stomach 60 min after intragastric administration. These results suggest that gastrointestinal motility is extensively suppressed by minimal abdominal surgery as well as by anesthesia.

Abdomen↗
PubMed2002

Evaluation of the barostat for recordings of gastrointestinal motility.

BACKGROUND: The barostat has been used to investigate gastrointestinal motility. No detailed technical evaluation to characterize the properties of this device for motility recordings has been reported. We, therefore, aimed to test the barostat in vitro under standardized conditions. METHODS: Barostat and manometry recordings were performed using a combined catheter in a pressure chamber. Some of the experiments were made in pig sigmoid colon in order to mimic recordings in a hollow organ. Data are mean +/- SD. RESULTS: Baseline changes of the bag volume under constant conditions were 3.9 +/- 2.0%. The bag volume increased by 4.5 +/- 1.1% with a temperature increase from 22 to 37 degrees C (p < 0.05). At external pressures above the bag operating pressure, the barostat bag collapsed, while only minimal volume reductions occurred at external pressures below the bag pressure. Barostat recordings of pressure events were delayed when compared with manometry and not linearly related to the pressure increases. CONCLUSION: The influence of temperature changes on barostat recordings is small. The volume decrease in the barostat bag is not linearly related to the external pressure increase and influenced by the operating pressure in the bag. This experimental study provides insight and caveats for those planning to use the barostat device for motility recordings of the gastrointestinal tract.

Animals↗