Contractions Of Small Intestine Research Articles

Motor patterns and propulsion in the rat intestine in vivo recorded by spatio‐temporal maps

We have used spatio-temporal maps derived from video images to investigate propagated contractions of the rat small intestine in vivo. The abdomen, including an exteriorized segment of jejunum, was housed in a humid chamber with a viewing window. Video records were converted to spatio-temporal maps of jejunal diameter changes. Intraluminal pressure and fluid outflow were measured. Contractions occupied 3.8 +/- 0.2 cm of intestine and propagated anally at 3.1 +/- 0.2 mm s(-1) when baseline pressure was 4 mmHg. Contractions at any one point lasted 8.7 +/- 0.6 s. Contractions often occurred in clusters; within cluster frequencies were 2.28 +/- 0.04 min(-1). Pressure waves, with amplitudes greater than about 9 mmHg, expelled fluid when the baseline pressure was 4 mmHg. In the presence of L-NAME, circular muscle contractions occurred at a high frequency, but they were not propagated. We conclude that video recording methods give good spatio-temporal resolution of intestinal movement when applied in vivo. They reveal neurally-mediated propulsive contractions, similar to those previously recorded from intestinal segments in vitro. The propagated contractions had speeds of propagation that were slower and frequencies of occurrence that were less than speeds and frequencies of slow waves in the rat small intestine.

Nitric oxide synthase inhibition results in immediate postoperative recovery of gastric, small intestinal and colonic motility in awake rats

Nitric oxide (NO) is known to inhibit gastrointestinal motility. However, no detailed analysis of gastric, small intestinal and colonic motor effects, including effects on contraction frequency, has, as yet, been reported after NO inhibition in awake rats. We therefore investigated the effects of NO synthase inhibition on gastric, small intestinal and colonic motility in awake rats under baseline conditions and in a postoperative ileus model. In Sprague-Dawley rats, strain gauge transducers were sutured either to the gastric corpus, the small intestine or the colon. After 3 days, L-NMMA (NO synthase inhibitor), D-NMMA or vehicle was given i.v., while the motility was recorded continuously. In addition, postoperative gastric, small intestinal or colonic motility was investigated after L-NMMA or vehicle treatment prior to abdominal surgery. The motility index, the contraction amplitude, the area under the contraction amplitude and the contraction frequency were analysed. L-NMMA decreased gastric motility to 60+/-8% for about 15 min, but continuously increased small intestinal motility to 221+/-22% and colonic motility to 125+/-7% compared to baseline (baseline=100%; p<0.01 for all comparisons). L-NMMA increased the contraction frequency throughout the gastrointestinal tract (stomach, 13+/-2%; small intestine, 8+/-1%; colon, 16+/-5%; p<0.01 vs. baseline for all comparisons). L-NMMA injection prior to surgery did not prohibit intraoperative inhibition of gastrointestinal motility, but did result in immediate recovery of gastric, small intestinal and colonic motility postoperatively (L-NMMA vs. vehicle, 0-60 min postoperatively; stomach, 90+/-9% vs. 53+/-3%; small intestine, 101+/-5% vs. 57+/-3%; colon, 134+/-6% vs. 60+/-5%; p<0.01 for all comparisons; no significant difference between preoperative baseline motility and L-NMMA treated rats postoperatively). Under baseline conditions, endogenous NO inhibits small intestinal and colonic motility and gastric, small intestinal and colonic contraction frequency in awake rats. In the early postoperative period, endogenous NO is a major inhibitory component that seems to constitute the common final pathway of mediators and the neural pathways inhibiting gastrointestinal motility in rats.

Guanosine 3',5'-cyclic monophosphate: a tapeworm-secreted signal molecule communicating with the rat host's small intestine.

Tapeworms alter the physiological environment of the host's small intestinal lumen by contracting the intestinal smooth muscle, thereby slowing the transit of intestinal contents. We hypothesize that parasite-to-host molecular signaling is responsible for the specific patterns of small intestinal smooth muscle contraction observed both during tapeworm infection and after the infusion of tapeworm-secreted molecules into the intestinal lumen of unanesthetized rats. Of the tapeworm-secreted compounds tested, only lumenal infusion of guanosine 3',5'-cyclic monophosphate (cGMP) induced contractile patterns that mimic those observed during tapeworm infection. The response to cGMP occurred in a concentration-dependent fashion. Our study clearly demonstrates that cGMP can serve as an extracellular signal molecule regulating small intestinal motility mechanisms in vivo.

Role of prostaglandins in lipopolysaccharide effects on K+-induced contractions in rabbit small intestine.

The mediators of the pathophysiologcal symptoms of septic shock are not completely understood. The aim of this work was to investigate the effect of lipopolysaccharide (LPS) on the K+-induced response of longitudinal segments of rabbit small intestine in vitro and the possible role of prostaglandins. Rabbits were treated with intravenously injected LPS. After 90 min animals were killed and intestinal segments were mounted in an organ bath. Lipopolysaccharide (0.2 microg kg-1) inhibited K+-induced contractions (60 mm) by 68% in duodenum, 58% in jejunum and 52% in ileum. Indomethacin antagonized LPS actions when injected 15 min before LPS. PGE2 reduced K+-induced contractions, imitating LPS effects. In contrast, contractions induced by K+ increased when intestinal segments were incubated in vitro with LPS for 90 min. The LPS (0.3 microg mL-1) increased K+-induced contractions (60 mm) by 46% in duodenum, 63% in jejunum and 85% in ileum. The LPS effect was antagonized by indomethacin at 10-6 m in duodenum and jejunum and at 10-8 m in ileum. PGE2 evoked dose-dependent contractions when added to the bath in duodenum, jejunum and ileum. These results suggest that effect of LPS on K+-induced contractions in the rabbit small bowel may be mediated by prostaglandin E2.

PAR-2 agonists induce contraction of murine small intestine through neurokinin receptors.

Protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor and is expressed throughout the gut. It is well known that PAR-2 participates in the regulation of gastrointestinal motility; however, the results are inconsistent. The present study investigated the effect and mechanism of PAR-2 activation on murine small intestinal smooth muscle function in vitro. Both trypsin and PAR-2-activating peptide SLIGRL induced a small relaxation followed by a concentration-dependent contraction. The sensitivity to trypsin was greater than that to SLIGRL (EC50 = 0.03 vs. 40 microM), but maximal responses were similar (12.3 +/- 1.6 vs. 13.7 +/- 1.3 N/cm2). Trypsin-evoked contraction (1 microM) exhibited a rapid desensitization, whereas the desensitization of response to SLIGRL was less even at high concentration (50 microM). Atropine had no effect on PAR-2 agonist-induced contractions. In contrast, TTX and capsaicin significantly attenuated those contractions, implicating a neurogenic mechanism that may involve capsaicin-sensitive sensory nerves. Furthermore, contractions induced by trypsin and SLIGRL were reduced by neurokinin receptor NK1 antagonist SR-140333 or NK2 antagonist SR-48968 alone or were further reduced by combined application of SR-140333 and SR-48968, indicating the involvement of neurokinin receptors. In addition, desensitizing neurokinin receptors with substance P and/or neurokinin A decreased the PAR-2 agonist-evoked contraction. We concluded that PAR-2 agonists induced a contraction of murine intestinal smooth muscle that was mediated by nerves. The excitatory effect is also dependent on sensory neural pathways and requires both NK1 and NK2 receptors.

Reactive oxygen species (ROS) generated in vitro decreases human small intestinal muscle contractions and inhibitory neuromuscular transmission

Reactive oxygen species (ROS) generated in vitro decreases human small intestinal muscle contractions and inhibitory neuromuscular transmission

Reactive oxygen species (ROS) generated in vitro decreases human small intestinal muscle contractions and inhibitory neuromuscular transmission

Reactive oxygen species (ROS) generated in vitro decreases human small intestinal muscle contractions and inhibitory neuromuscular transmission

Connections between P 2 purinoceptors and capsaicin-sensitive afferents in the intestine and other tissues

Relations between P 2 purinoceptors and capsaicin-sensitive sensory neurons include an excitatory action of P 2 purinoceptor agonists on spinal afferent neurons, as well as release of ATP from afferents at their central and peripheral endings, and a possible participation of ATP in nociception and/or in `local efferent' responses mediated by sensory nerves at the periphery. The present paper briefly summarizes available evidence on these interrelations. Ample evidence shows that ATP and other P 2 purinoceptor agonists can activate primary afferent neurons, through P2X 3 receptors and probably other purinoceptors as well, but evidence for an involvement of P 2 purinoceptors in nociception or in `local efferent' responses due to activation of primary afferents is, at best, circumstantial. The possibility is also dealt with that P 2 purinoceptor activation may cause small intestinal contraction with the mediation of capsaicin-sensitive sensory neurons and that the motor response to capsaicin in this tissue may involve the release of a P 2 purinoceptor stimulant from sensory nerves. Our data show that cholinergic contractions of the guinea-pig ileum in response to the P 2 purinoceptor agonist α,β-methylene ATP (α,β-meATP) are blocked by atropine, but not by in vitro capsaicin pretreatment (which completely blocks the contractile action of capsaicin). Cholinergic ileum contractions due to capsaicin (2 μM) are insensitive to suramin (a P 2 purinoceptor antagonist; 100 μM). In the presence of antagonists acting at tachykinin NK 1 and NK 2 receptors, however, suramin (100 μM) causes a significant inhibition of the capsaicin-evoked contraction. These data indicate that capsaicin-sensitive nerves are not involved in the excitatory effect of α,β-methylene ATP on myenteric neurons. On the other hand, ATP is probably involved in the `non-tachykininergic' component of the capsaicin-induced excitatory response of the small intestine. ATP may originate from sensory neurons and probably acts as activator of myenteric nerves.

Canine small bowel motor patterns and contractions are not neurally regulated during enteric nutrient infusion.

The aims of this study were to determine the effects of duodenal and jejunoileal nutrient infusions on small intestinal motor patterns and intestinal contractions in neurally intact and neurally isolated small bowel. Fifteen dogs were prepared with duodenal and jejunal infusion and manometry catheters and a diverting jejunal cannula. Ten of the dogs underwent in situ neural isolation of the jejunoileum. A mixed nutrient meal (0.5 kcal/ml) was infused into the duodenum or jejunum at 3 ml/min for 5 h. Control experiments involved infusion of a balanced salt solution. Manometric data collected on-line to a microcomputer were analyzed for direction, distance, and velocity of spread of single pressure waves (SPW) and clustered contractions. Isolated duodenal and jejunoileal nutrient infusions inhibited the fasting motor pattern in neurally intact and neurally isolated small bowel. Motor activity (motility index) increased slightly during nutrient infusion within groups, but there were few differences between groups. Neither neural isolation nor nutrient infusion had a consistent effect on spread of SPW or migration of clustered contractions. Isolated duodenal and jejunoileal nutrient infusions in the dog inhibit fasting motor patterns and increase motor activity slightly but have little effect on characteristics of individual and clustered contractions. Extrinsic innervation to the jejunoileum or intrinsic neural continuity of the jejunum with the duodenum had little effect on single or grouped contractions. Although the changes in motor activity demonstrated in this study appear small, alterations in intestinal transit and absorption may still occur and may be of importance physiologically.

Inhibition of Antigen‐Induced Muscle Contractions by‐Inhibitors of Thromboxane Pathway in Rat Small Intestine

Rats were sensitized against egg albumin and the response of the longitudinal muscle from the proximal small intestine to the antigen was tested. Egg albumin (1-100 micrograms/ml) concentration-dependently induced a contraction of the longitudinal muscle in tissues from sensitized animals but not from nonsensitized animals. The response to the antigen was resistant to neuronal blockers like tetrodotoxin, atropine and hexamethonium. Inhibitors of thromboxane synthesis such as the cyclooxygenase inhibitor, indomethacin, the thromboxane synthase blocker, 1-benzylimidazole, or the combined cyclooxygenase/lipoxygenase/thromboxane synthase inhibitor, sulfasalazine, inhibited the contraction evoked by egg albumin. A similar concentration-dependent inhibition of the antigen response was observed with two thromboxane A2 receptor blockers, SK&F 88046 and KW-3635. None of these blockers affected the response to the muscarinic agonist, carbachol, excluding unspecific effects of the drugs on smooth muscle contractility. The effect of antigen was reduced by the mast cell stabilizing agent, quercetin, and by the histamine H1 receptor blocker, mepyramin. These drugs, however, also inhibited the response to carbachol. When contractions were stimulated directly by the stable thromboxane derivative, carbocyclic thromboxane A2, the smooth muscle proved to be more than three orders of magnitude more sensitive to this agonist of the thromboxane pathway compared to histamine. Consequently, thromboxane A2 seems to be one of the main mediators of anaphylactically induced longitudinal muscle contractions in the rat small intestine.

Jejunoileal transplantation

This study was designed to determine if extrinsic innervation and intrinsic neural continuity with the duodenum (neuroenteric physiologic pathways disrupted during intestinal transplantation) modulate the characteristics of interdigestive motor activity in the canine small bowel. Five dogs served as neurally intact controls (group 1) and 10 dogs (group 2) underwent a model of jejunal autotransplantation involving in situ neural isolation of the jejunoileum. Fasting duodenal and jejunal motor activity was recorded on-line to a microcomputer using closely spaced duodenal and jejunal manometry catheters. Characteristics of global motor patterns, the migrating motor complex (MMC), and local motor patterns, including individual contractions and grouped clustered contractions, were determined. Neural isolation of the jejunoileum disrupted coordination of duodenal and jejunal phase III activity, increased the variability of cycling of the MMC, decreased the period of the jejunal MMC, and increased motility indices in the neurally isolated jejunum. In contrast, single pressure waves and clustered contractions in the neurally isolated jejunum were not altered significantly in incidence or direction, distance, or velocity of spread. In situ neural isolation of the jejunoileum leads to temporal dissociation of the MMC between the transplanted segment (jejunum) and the duodenum but does not appear to alter markedly the characteristics of local contractile activity as measured by individual or grouped contractions. The occurrence of interdigestive jejunal motor patterns and the local organization of individual and grouped small intestinal contractions are not controlled by extrinsic innervation or intrinsic neural continuity with the duodenum.

P2-102 - GM-611, an acid-stablc erythromycin A derivative, induces contractions in the rabbit small intestine via the motiiin receptor

P2-102 - GM-611, an acid-stablc erythromycin A derivative, induces contractions in the rabbit small intestine via the motiiin receptor

Nitric oxide induces acetylcholine-mediated contractions in the guinea-pig small intestine.

In longitudinal muscle/myenteric plexus preparations of the guinea-pig ileum, exogenous nitric oxide (NO) induced concentration-dependent relaxations. In tissues at basal tone, NO (3 x 10(-6) M) induced a moderate relaxation followed by a pronounced contraction, consisting of a quick and sustained component. Tetrodotoxin (5 x 10(-7) M) abolished both phases of the contraction. Atropine (5 x 10(-7) M) abolished the quick component and reduced the sustained component of the contraction; the latter was further suppressed by the selective NK1 receptor antagonist CP 96,345. Hexamethonium (5 x 10(-5) M) failed to affect the contractile response to NO. It is concluded that administration of exogenous NO in the guinea-pig ileum can lead to activation cholinergic and to a lesser degree tachykininergic neurones.

Human small intestinal contractions and aboral traction forces during fasting and after feeding.

Small intestinal intraluminal pressure activity and aboral traction forces were explored in 19 healthy volunteers using a combined manometry and traction force detecting assembly sited in the upper small intestine. Each aboral traction event was classified as being associated with either a propagating or a stationary contraction and its force measured. During phase I no contractions or traction events were seen. During phase II, traction events related to propagating contractions mean (SEM) (2.2 (0.2)/min) and to stationary contractions (0.3 (0.1)/min) generated similar force/event (7.5(0.9 g v 8.7 (1.4) g, p > 0.05). During phase III, all traction events were related to propagating contractions and generated 9.3 (2.4) g force/event (p > 0.05 v phase II). After feeding, traction events related to propagating contractions generated similar force/event to those related to stationary contractions (5.9 (1.0) g v 9.3 (2.7) g, p > 0.05 v each other and v fasting). No consistent pattern was seen in the temporal distribution of the traction events or in the pattern of the amplitude of the force of successive traction events.

Intestinal motor function in irritable bowel syndrome.

Irritable bowel syndrome is widely considered to be associated with disordered gastro-intestinal motility. The evidence for a motor disorder in the colon and small intestine of patients with irritable bowel syndrome is reviewed. Results of myoelectric, motility and transit studies in both the colon and small intestine are inconsistent. Difficulties in interpreting colonic motility have led investigators to address the small intestine as a possible site of dysmotility. An increase in the number of clustered contractions in the proximal small intestine has been reported by some, but not all investigators. Methodological differences as well as patient selection, symptom severity and fluctuation may all contribute to discrepancies between the results of different studies. Motility disturbances may be present which are currently unrecognised due to an inadequate understanding of the propagation of colonic contractions, and of small intestinal contractions during phase II and postprandially. Whether the reported motor disturbances arise locally in the gut or originate from higher centres in the central nervous system has not been established.

Galanin receptor in plasma membrane of canine small intestinal circular muscle

High-affinity binding sites for galanin were identified and characterized in plasma membrane of circular muscle from canine small intestine using 125I-radioiodinated synthetic porcine galanin. Scatchard analysis indicated a high-affinity binding site on plasma membrane with a dissociation constant (Kd) of 0.58 nM and a binding capacity of 389 fmol/mg. Unlabeled galanin or NH2-terminal galanin fragments competitively inhibited the binding of 125I-galanin in a concentration-dependent manner, whereas the COOH-terminal fragment was inactive. Computer analysis of competitive binding data suggested a two-site model with a high-affinity (inhibitor constant, Ki = 0.01 nM) and a low-affinity (Ki = 2.8 nM) binding site. Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) enhanced the dissociation of bound 125I-galanin. Cholera toxin (CTX) and GTP gamma S abolished the activity of the high-affinity binding site, leaving the low-affinity binding site. We conclude that galanin may act as an neurotransmitter to inhibit canine small intestinal smooth muscle contraction by interaction with a CTX-sensitive G protein-coupled specific receptor on muscle membrane. This receptor showed different G protein coupling from a synaptosomal receptor previously described in the same tissue preparations.

Gastrointestinal longitudinal muscle contractions.

The patterns of longitudinal muscle contractions of the stomach and the small intestine and their relationship with circular muscle contractions during the fasting and the fed state were investigated in conscious dogs. In the stomach, the longitudinal muscle contracted in a 1:1 relationship with the circular muscle contractions. There was no significant difference between the frequency, duration, and time of onset of gastric longitudinal and circular muscle contractions, and their amplitudes were significantly correlated with each other. In the small intestine when the circular muscle contracted, the longitudinal muscle exhibited passive elongation during the fasting and the fed state. There was no significant difference between the onset, duration, and frequency of small intestinal circular muscle contractions and the passive longitudinal muscle elongations; their amplitudes were strongly correlated with each other. During a circular muscle giant migrating contraction, the longitudinal muscle exhibited a monophasic contraction, initially a contraction followed by passive elongation or a pure passive elongation. During a retrograde giant contraction, the longitudinal muscle exhibited only a pure monophasic contraction or a contraction-elongation complex. These data suggest that the enteric nerves in the small intestine innervate the two muscle layers in a reciprocal fashion and those in the stomach in a complementary fashion.

Effects of cholinoceptor and 5-hydroxytryptamine3 receptor antagonism on erythromycin-induced canine intestinal motility disruption and emesis.

1. Erythromycin administration is associated with gastrointestinal problems, disturbed gastrointestinal motility and emesis. This study in the dog investigates the underlying mechanisms. 2. Intestinal myoelectrical activity and the occurrence and latency of emesis were recorded in eight conscious dogs. All drugs were administered intravenously. 3. Erythromycin (7 mg kg-1) increased contractions of the proximal small intestine, and caused emesis in all fasted dogs and in 5 dogs after food. Atropine (50 mg kg-1 min-1) and hexamethonium (10 mg kg-1 h-1) partially inhibited the GI motility effects but did not significantly reduce emesis. 4. Metoclopramide at a high dose (2 mg kg-1 h-1) reduced the incidence of emesis in the presence of increased intestinal motility, but a low dose (150 micrograms kg-1 h-1) was ineffective. 5. A 5-hydroxytryptamine3 (5-HT3) receptor antagonist, MDL 72222 (1 mg kg-1), reduced emesis when given alone and combined with metoclopramide (low dose). The 5-HT4 receptor agonist BRL24924 (Renzapride, 1 mg kg-1) had no effect on emesis either alone in combination with metoclopramide. 6. In conclusion, erythromycin-induced GI motility disturbances and emesis are not causally related. Whereas the increase in intestinal smooth muscle activity is possibly cholinergically mediated, emesis occurs at least in part via a 5-hydroxytryptaminergic mechanism, but does not involve the dopamine system.

Gastrointestinal motor effects of erythromycin in humans

The effects of an antibacterially effective IV dose of erythromycin on gastrointestinal motor activity were investigated in eight normal healthy human volunteers in the fasted state and the fed state. Motor activity was recorded by a multilumen manometric tube. Data were analyzed visually and by a computer method. Blood samples were obtained for erythromycin and motilin assays. In the gastric antrum, erythromycin significantly increased the total duration, amplitude, and area under contractions from 0 to 60 minutes and frequency of contractions from 0 to 30 minutes from the start of its infusion in the fasted state. A similar response in the fed state occurred mostly from 0 to 30 minutes after the start of erythromycin infusion. By contrast, erythromycin inhibited the frequency and decreased the duration of small intestinal contractions in the fed state but had no effect in the fasted state. The gastric motor response was related to the plasma concentration of erythromycin, but not to plasma motilin. Erythromycin significantly shortened the duration of migrating motor complex disruption by a meal. Erythromycin also induced symptoms of upper abdominal pain, bloating, and nausea. Abdominal pain was related to strong antral contractions in both fasted and fed states; bloating occurred only in the fed state. Nausea occurred in both fasted and fed states, but it was not related to any specific pattern of motor activity. It is concluded that the strong antral contractions induced by erythromycin may accelerate the rate of gastric emptying, but they may also be responsible for causing the sensations of upper abdominal pain and bloating. The motor response to erythromycin is less during the fed than during the fasted state. The strong antral contractions induced by erythromycin are not mediated by the release of motilin.

Effect of GABA on the contratility of small intestine isolated from rat

This study was designed to investigate the effect of GABA and related substances on the spontaneous contraction of rat small intestine. The rats(Sprague-Dawley), weighing 200-250g, were sacrificed by cervical dislocation, and the small intestine was isolated. Longitudinal muscle strips from duodenum, jejunum and ileum were suspended in Biancani's isolated muscle chambers and myographied isometrically. GABA and muscimol, a GABA A receptor agonist relaxed the duodenum and jejunum significantly, but baclofen-induced relaxation in those muscle strips was negligible. The effectiveness of GABA and muscimol in various regions were the greatest on duodenum, and greater on jejunum than on ileum The effect of GABA and muscimol was antagonized by bicuculline, a compeptitive GABA A receptor antagonist and picrotoxin, a noncomptitive GABA A receptor antagonist. Duodenal relaxation induced by GABA and muscimol was unaffected by hexamethonium, but was prevented by tetrodotoxin. These results suggest that GABA inhibit the contractility of smooth muscle with distinct regional difference of efficacy, and the site of inhibitory action is the GABA A receptor existing at the presynaptic membrane of postganglionic excitatory nerves.