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GLP-1 and GLP-2 act in concert to inhibit fasted, but not fed, small bowel motility in the rat.

Small bowel motility was studied in rats at increasing (1-20 pmol/kg/min) intravenous doses of either glucagon-like peptide-1 (GLP-1) or glucagon-like peptide-2 (GLP-2) alone, or in combination in the fasted and fed state. There was a dose-dependent inhibitory action of GLP-1 on the migrating myoelectric complex (MMC), where the dose of 5 pmol/kg/min induced an increased MMC cycle length. No effect was seen with GLP-2 alone, but the combination of GLP-1 and GLP-2 induced a more pronounced inhibitory effect, with significant increase of the MMC cycle length from a dose of 2 pmol/kg/min. During fed motility, infusion of GLP-1 resulted in an inhibition of spiking activity compared to control. In contrast, infusion of GLP-2 only numerically increased spiking activity compared to control, while the combination of GLP-1 and GLP-2 resulted in no change compared to control. In summary, this study demonstrates an additive effect of peripheral administration of GLP-1 and GLP-2 on fasted small bowel motility. In the fed state, GLP-1 and GLP-2 seem to display counter-balancing effects on motility of the small intestine.

Animals↗

Effect of pituitary adenylate cyclase-activating polypeptide on exocrine and endocrine secretion in the ovine pancreas.

The role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the regulation of exocrine and endocrine pancreas was investigated in conscious sheep. Intravenous infusions of PACAP-27 and PACAP-38 (1, 3, and 10 pmol/kg/min) for 10 min during phase II of the duodenal migrating myoelectric complex accelerated pancreatic protein and amylase outputs dose-dependently. The responses in enzyme secretion to both PACAPs at the highest doses were inhibited significantly by atropine infusion (14.4 nmol/kg/min). Vasoactive intestinal polypeptide (VIP) at 3 pmol/kg/min significantly accelerated protein but not amylase outputs, although the response to the highest dose was not significantly influenced by atropine. PACAP-27 and VIP increased pancreatic juice flow and bicarbonate output dose-dependently; however, the responses to the highest dose were not altered significantly by atropine. On the other hand, intravenous injection of PACAP-38 (100 pmol/kg) did not influence basal plasma concentration of insulin, glucagon, and glucose. Moreover, PACAP-38 (1-100 pmol/kg) altered neither pancreatic endocrine response to intravenous infusion of glucose (20 mumol/kg/min) not that to n-butyric acid (33 mumol/kg/min). These results suggest that PACAP contributes to the regulation of exocrine secretion of the ovine pancreas but not to endocrine secretion. PACAP appears to accelerate pancreatic enzyme secretion mostly via the cholinergic nerves.

Animals↗

Gastro-duodenal motor and transit disturbances associated with Haemonchus contortus infection in sheep.

Abomasal and duodenal motility was investigated by electromyography in 4 lambs fitted with permanent abomasal and duodenal cannulae and infected twice with 25,000 Haemonchus contortus larvae at an interval of 39 days. In addition, abomasal and duodenal pH, flow rate of digesta of the duodenum, and faecal water content were determined. The 80-90 min cycles of antral contractions were shortened for at least 3 weeks after infection. This was accompanied by a 26% increase in the number of duodenal migrating myoelectric complexes/day during the intraparietal development of the larvae (10-12 days). Concomitantly, the duodenal flow of digesta increased from 215 +/- 22 ml/h to 318 +/- 15 ml/h 4 days after infection and was associated with a higher water content of the faeces. The frequency of the migrating myoelectric complexes, but not the duration of antral motor cycles (or the duodenal flow rate), was correlated with both gastric (P less than 0.01) and duodenal (P less than 0.05) pH after the first and second infections. The duodenal flow rate was correlated with the Cl- concentrations of the abomasal contents (P less than 0.01) and with the duodenal pH (P less than 0.05). It is concluded that, (i) the duodenal motor disturbances associated with experimental H. contortus infection are related to the alterations in abomasal gastric acid secretion which occurs during the histotrophic phase of larval development and (ii) the increased duodenal flow is a consequence of ionic permeability changes of the gastro-intestinal mucosae.

Abomasum↗

The influence of a chronic subclinical infection of Trichostrongylus colubriformis on gastrointestinal motility and digesta flow in sheep.

The influence of a chronic subclinical infection of Trichostrongylus colubriformis, 2500 larvae/day for 12 weeks, on gastrointestinal motility and digesta flow was studied in 12 sheep supplied ad libitum with food and water. Motility was recorded by X-radiography and electromyography from chronically implanted electrodes; abomasal volume and outflow were estimated by dilution of CrEDTA; small intestinal transit time was estimated by passage of Phenol Red. The findings were compared with measurements made prior to infection at restricted food intake and reported separately. The first effects of infection were seen after 3-4 weeks. No animal developed diarrhoea, but food intake was progressively reduced. Small intestinal transit time, abomasal volume and half-time of marker dilution increased while abomasal outflow decreased during infection. These changes occurred both in absolute terms and when compared with values predicted from the observed level of food intake. As the animals became resistant to the parasites abomasal volume and digesta flow returned towards control values (weeks 10-12). The migrating myoelectric complex (MMC) was disrupted in only one sheep, and only transiently. In all sheep the frequency of the MMC was increased during infection and there was a progressive inhibition of abomasal, duodenal and jejunal motility. X-radiography showed there was prolonged pooling of digesta in the proximal small intestine which was cleared only at the phase of regular spiking activity. Two sheep given an anthelmintic drench recovered normal motility and clearance of digesta. It is concluded that subclinical infection of sheep with T. colubriformis alters the normal pattern of gastrointestinal motility in the absence of any diarrhoea, and causes inhibition of abomasal and proximal small intestinal motility and digesta flow. The increased frequency of MMCs helps to maintain digesta flow through the proximal small intestine.

Abomasum↗

Reversed bowel segments for the treatment of short bowel syndrome: assessment of their minimal length in correlation with electromyographic pattern in the rat.

Reversal of a distal intestinal loop is a surgical therapy intended to cure rapid intestinal transit in short bowel syndrome. To be active, a reversed loop must present a retrograde propagation of electromyographic patterns and must not be so long as to cause total obstruction. The aim of the current study was to propose methods to calculate the minimal length of the intestinal reversed loop taking into consideration the two previous conditions. Intestinal electromyograms were recorded in 65 rats at short-term (4 days after surgery) and ten rats at long-term (50 days after surgery). Control rats demonstrated that the preprandial regular spiking activity (RSA) of the migrating myoelectrical complex (MMC) extended simultaneously a definite part of the intestine which corresponds to the minimal length to reverse. A similar result can be obtained from a trigonometric representation. Whatever the method, the minimal lengths allowing the recording of RSA decreased along the rat intestine from 6 cm (proximal jejunum) to 4 cm (distal ileum). The experiments demonstrated that shorter loops did not present the preprandial RSA. In conclusion, the minimal reversed length depends on intestinal electromyographic parameters and, thereby, on the intestinal level.

Animals↗

Intestinal and colonic motor alterations associated with irradiation-induced diarrhoea in rats.

Localized application of ionizing radiation to the gastrointestinal tract frequently elicits responses, which include diarrhoea. The origin of this symptom is not clear but has been attributed to loss of epithelial integrity, together with alterations in motility and increased secretion. The purpose of this study was to examine whether a 10 Gy abdominal gamma irradiation leads to an inflammatory reaction, and to compare intestinal and colonic motility in controls and abdominally irradiated rats 1, 3 and 7 days after irradiation, using an electromyographic technique. The motility parameters analysed were the frequency and velocity of propagation of migrating myoelectric complexes (MMC) in the jejunum and colonic spike activity (long spike bursts; LSB) per 10 min in fasted rats. The MMC frequency was significantly reduced on days 1 and 7 after irradiation and the MMC pattern was markedly disrupted on day 3. The frequency of colonic LSB was significantly reduced on days 1, 3 and 7. Mouth to anus transit was significantly accelerated on day 3 only and diarrhoea was observed at this time. Myeloperoxidase activity in the jejunum and colon was also increased on this day only. It is concluded that irradiation-induced diarrhoea occurs contemporaneously with disruption of MMC in the small intestine.

Animals↗

Role of NK2 receptors in gastric barosensitivity and in experimental ileus in rats.

This study was performed to evaluate the role of tachykinin NK2 receptors in gastric barosensitivity and in postsurgical intestinal atony, using a selective NK2 antagonist (MEN 11420). Gastric distensions were performed in rats equipped with a gastric balloon and electrodes implanted in the neck muscles. Ileus was produced by laparotomy and caecum palpation in rats previously prepared with electrodes implanted on the proximal jejunum. Fifteen minutes before gastric distension or laparotomy, the animals received MEN 11420 (10, 100 or 200 microg kg-1 intravenously) or saline. The first distending pressure to increase the integrated neck electromyogram > 100% was considered the pain threshold. MEN 11420 (100 microg kg-1) increased significantly pain threshold (20.5 +/- 1.2 vs. 17.0 +/- 0.8 mm Hg) but did not modify gastric volumes at the three doses tested. Abdominal surgery was followed by a total inhibition of jejunal spiking activity lasting 80.4 +/- 18.7 min. MEN 11420 (10 and 100 microg kg-1) shortened the duration of motor inhibition by 36 and 39%, and induced a premature recovery of the phase III of migrating myoelectric complex at the lowest dose tested (130 +/- 32 vs. 192 +/- 28 min). We conclude that NK2 receptors, probably located on afferent fibres, are involved in gastric barosensitivity and in postsurgical intestinal atony.

Adrenergic alpha-Antagonists↗

Enhanced intestinal motor response to cholecystokinin in post-Nippostrongylus brasiliensis-infected rats: modulation by CCK receptors and the vagus nerve.

The jejunal inflammation induced in rats by the nematode Nippostrongylus brasiliensis is followed by intestinal neuroimmune alterations including mast cell hyperplasia and nerve remodelling. On the other hand, cholecystokinin (CCK) plays a pivotal role in the regulation of intestinal motility. The aim of this study was to determine whether the intestinal motor response to CCK is altered 30 days after infection by N. brasiliensis. Thus, CCK-8 (50 microg kg(-1) intraperitoneally) disrupted the pattern of jejunal migrating myoelectric complexes for a longer time in postinfected rats (95.5 +/- 3.5 min) than in controls (48.1 +/- 5.1 min). This enhanced jejunal response was also found after oral administration of the potent releaser of endogenous CCK, soybean trypsin inhibitor. In contrast, no alteration of the inhibition of colonic motility by CCK administration was observed. The increased responsiveness of jejunal motility to CCK persisted after mast cell stabilisation or depletion but was prevented by atropine, devazepide and L-365260 (CCK-A and CCK-B receptor antagonists, respectively) and vagotomy. These results indicate that neuroimmune alterations after N. brasiliensis infection lead to an increased intestinal motility response to CCK that involves a cholinergic mediation, a vagal pathway and alterations in intestinal CCK-A and CCK-B receptors.

Animals↗

Patterns of electrical activity in the digestive tract of the conscious cat.

1. Bipolar electrodes were permanently implanted on the gastric antrum, and on the different portions of the small intestine of each of eleven healthy adult cats receiving one meal daily. All parts of the feline gut exhibited, as in several other species, regular slow waves and alternate periods of quiescence and electrical spiking activity during the recording sessions lasting from 10 to 30 d. 2. Patterns of electrical activity characteristic of this species were identified. Both the amplitude and frequency of the antral slow-wave were related to the presence of superimposed spike bursts during fasting. A decrease in the antral slow-wave frequency and increase in the length of the duodenal plateau of slow waves after the daily meal were related to its nature. 3. In fasted state, the electrical spiking activity of the small intestine occurred as fused spike bursts of large amplitude potentials migrating slowly over short distances only 24 h after feeding. They are interspersed with short periods of irregular spiking activity. 4. These findings suggested that, except the distal part of the small intestine which showed an activity which resembled partially the migrating myoelectric complex observed in other species during the fasting state, the motility patterns of the digestive tract in the cat were not comparable to those observed in the dog or sheep. In the cat, mixing of the contents seemed to result from more or less regular spiking activity allowing their propulsion distally. The propagation over distances varying from 200 to 1000 mm of nine to eighteen daily fused spike bursts in the fasting state remains unclear but they are related to the digestive function in accordance with the displacement aborally of their origin in a prolonged fasting condition.

Action Potentials↗

The relation between food intake and abomasal emptying and small intestinal transit time in sheep.

The relation between the level of food intake and gastrointestinal motility and digesta flow in the abomasum and small intestine was studied in sheep fitted with nichrome-wire electrodes in the gut wall, an abomasal and a duodenal catheter and a terminal ileal cannula. Abomasal volume and outflow were calculated from CrEDTA dilution in six sheep and small intestinal transit time by the passage of Phenol Red in ten sheep. The frequency of the migrating myoelectric complex of the small intestine was not altered by the level of food intake but the duration of the periods of irregular spiking activity, the amplitude of abomasal activity and the frequency of duodenal rushes were decreased as the level of food intake was decreased. There was a linear relation between the level of food intake (FI) and abomasal outflow (mean with SEM: 327 (69) ml/h for each kg FI/d; P less than 0.01), and abomasal volume (mean with SEM: 344 (50) ml/kg FI per d; P less than 0.001), without any significant change in the half-time of marker dilution in the abomasum. Small intestinal transit time decreased with an increase in food intake (mean with SEM: -54.9 (5.6) min/kg FI per d; P less than 0.001). It is concluded that abomasal volume and the rate of digesta flow from the abomasum and along the small intestine are linearly related to the level of food intake.

Abomasum↗

Postoperative electromyographic profile in human jejunum.

The postoperative electromyographic profile of the proximal jejunum and its evolution during recovery from surgery were defined in fasted humans after cholecystectomy. An intraluminal probe supporting four groups of bipolar electrodes was transnasally inserted at the end of surgery to allow continuous recording of jejunal electrical activity over 4 consecutive days. Electromyographic activity was characterized by an early reappearance of phase 3 of migrating myoelectric complexes (MMC) lasting 5.2 +/- 0.6 minutes and occurring at 38.1 +/- 3.1-minute intervals at day 1 after surgery. During the 4 days after surgery, there was an increased duration of MMC, mainly consisting of phase 2 occurrence with an increased duration and lengthening of the MMC cycle. The amplitude of spikes during phase 3 increased. During the postoperative period, characterized by an inversion of the circadian rhythm, the velocity of propagation was higher (p less than 0.05) between 18:00 and 06:00 (4.0 +/- 0.5 cm/minute) than between 06:00 and 18:00 (3.1 +/- 0.3 cm/minute). In contrast, the duration of phase 2 was lower during nighttime (18:00 to 06:00) than during daytime. The authors conclude that during the early (1 to 2 days) period after cholecystectomy, the jejunal electromyographic activity is limited to phase 3 activity, but that a normal fasted pattern is recovered after 4 days. A progressive reorganization and coordination of the intestinal tract may account for this delay.

Aged↗

Effects of medetomidine on intestinal and colonic motility in the dog.

The motor responses of the jejunum and colon to stimulation of alpha 2-adrenoceptors by medetomidine and clonidine were investigated in four dogs. In fasting dogs, medetomidine, at a dose rate of 30 micrograms/kg i.v., disrupted the migrating myoelectric complex (MMC) pattern of the small intestine for about 2 h. Similar, but shorter-lasting effects were also induced by clonidine (30 micrograms/kg i.v.) on the jejunum. The administration of alpha 2-agonists inhibited colonic motility in fasting dogs, although medetomidine-induced inhibition was preceded by a short period of increased muscle tone. All these effects were reversed by the alpha 2-antagonists atipamezole (0.15 mg/kg i.v.) and yohimbine (0.20 mg/kg i.v.). In fed dogs, medetomidine (30 micrograms/kg i.v.) induced a strong increase of the tone on the proximal colon, while the activity of the medium and distal colon was completely suppressed. Yohimbine (0.50 mg/kg i.v.) immediately restored the activity of the colon and induced a propagated giant contraction and defaecation by the animal. These data confirm the importance of alpha 2-adrenergic receptors in the control of intestinal and colonic motility in the dog.

Adrenergic alpha-Agonists↗

Neural mechanisms of early postinflammatory dysmotility in rat small intestine.

Although human postinflammatory dysmotility is known, so far animal studies have primarily investigated changes during inflammation. Here, we focused on postinflammatory changes in rat jejunal myenteric plexus and jejunal motility. Evolution of ethanol/2,4,6-tri-nitrobenzene sulphonic acid (TNBS)-induced inflammation was assessed histologically and by measuring myeloperoxidase activity (MPO). Electromyography and immunohistochemistry were performed 1 week after ethanol/TNBS and also after N(G)-nitro-L-arginine methyl ester (L-NAME) administration. Ethanol/TNBS induced a transient inflammation, with normalization of MPO and histological signs of an early phase of recovery after 1 week. The number of cholinergic neurones was not altered, but myenteric neuronal nitric oxide synthase (nNOS)-immunoreactivity was significantly lower in the early phase of recovery after TNBS compared with water (1.8 +/- 0.2 vs 3.5 +/- 0.2 neurones ganglion(-1), P < 0.001). Interdigestive motility was disrupted with a loss of phase 1 quiescence, an increase of migrating myoelectric complex cycle length, a higher number of non-propagated activity fronts and a decrease of adequately propagated phase 3 s after TNBS. Administration of L-NAME resulted in a similar disruption of interdigestive motility patterns. In the early phase of recovery after ethanol/TNBS-induced jejunal inflammation, a loss of motor inhibition occurs due to a decrease of myenteric nNOS activity. These observations may provide a model for early postinflammatory dysmotility syndromes.

Animals↗

Loss of forestomach motility in sheep experiencing ruminal lactic acidosis is not dependent on duodenal acidification by lactic acid.

Reticuloruminal motility, duodenal myoelectrical activity, and the pH and lactic acid concentrations of ruminal and duodenal contents were monitored in rumen fistulated sheep that were intraruminally loaded with finely ground wheat (50 g/kg). Following ruminal loading, reticuloruminal motility was enhanced. However, within 6 hours of loading, forestomach motility was impaired and within 9 hours ruminal stasis occurred. During loss of forestomach motility, lactic acid concentrations in ruminal contents increased and may, in part, have contributed to the decrease in pH of ruminal fluids. The levels of lactic acid within duodenal contents also rose, however, the pH of duodenal contents remained unchanged. During the loss of reticuloruminal motility, premature regular spiking activity (RSA) and/or abnormal patterns of migrating myoelectric complexes (MMC) were not observed on the duodenum. These findings indicate that loss of forestomach motility in ruminal lactic acidosis may not be a consequence of acidification of the proximal duodenum by lactic acid produced in the forestomach.

Acidosis, Lactic↗

Influence of substance P on gastrointestinal myoelectrical activity in the conscious piglet.

In conscious piglets with electrodes implanted in the wall of the antrum pylori, the small intestine and the caecum, the influence of intravenous infusion of substance P (SP) (0.1 and 1 micrograms/kg/min for 2 hours) on gastrointestinal myoelectrical activity and arterial pressure was studied. SP was without significant influence on electrical activity of the antrum. However, intestinal myoelectrical activities were significantly stimulated. In the small intestine SP infusion resulted in an increase in frequency of migrating myoelectrical complexes and in irregular spiking activity, resulting in an augmentation of the integrated total activity. In the caecum SP provoked a prolongation of complexes of long spike bursts (LSB) as well as an increase in number of LSB/complex. In the studied doses SP had no significant effect on arterial pressure.

Animals↗

Influence of motilin on gastrointestinal electrical activity in the conscious piglet.

In conscious just-weaned piglets, fed ad libitum, with electrodes implanted in the wall of the antrum pylori, duodenum, jejunum, ileum and caecum, infusion of motilin (2 and 20 ng/kg/min for 2h) induced a transient increase in the frequency of the fast oscillations in the antrum followed by a delayed decrease. The polypeptide, however, was unable to induce a premature or extra phase III activity or to change the frequency of the migrating myoelectrical complexes.

Animals↗

Effect of serotonin on gastrointestinal electrical activity in the conscious piglet.

In conscious piglets with electrodes implanted in the wall of the antrum pylori, duodenum, jejunum and ileum, the influence of intravenous infusion of serotonin (5-HT), 4 micrograms/kg/min for 2 hours, on gastrointestinal electrical activity and arterial pressure was examined. 5-HT was without significant influence on antral electrical activity and arterial pressure. In the small intestinal parts 5-HT provoked a shortening of the interval of the migrating myoelectrical complex (MMC) by reducing the duration of phase I and phase II activities, and an increase in propagation velocity. 5-HT also induced an increase in phase III activity. A possible involvement of 5-HT in the initiation and propagation of the MMC is suggested.

Animals↗

Effects of erythromycin on myoelectric activity of the spiral colon of dairy cows.

The effects of erythromycin on myoelectric activity of the spiral colon of dairy cows were investigated in a prospective study. Four Simmental x Red-Holstein crossbred cows of similar body weight and condition with seven pairs of bipolar electrodes implanted in the intestine (one each in the distal ileum, caecum and proximal colon, and four in the spiral colon) were included. Erythromycin lactobionate (1 mg kg(-1)) and 0.9% sodium chloride solution (NaCl) were administered to each cow in a random order. Erythromycin was diluted with NaCl and both treatments were administered slowly intravenously over a period of 5 min 1 h after onset of a phase III of the bovine colonic migrating myoelectric complex (bcMMC). A 3-6-day washout period was scheduled between trials. Significant differences between the results of the treatments were observed for spike duration in phase I as well as for spike duration and duration of spiking activity during phase II of the second bcMMC, which were significantly higher after erythromycin treatment than after NaCl. These findings suggest an indirect effect of erythromycin on colonic motility in cattle.

Animals↗