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PubMed2000

Development of the interstitial cell of Cajal: origin, kit dependence and neuronal and nonneuronal sources of kit ligand.

Kit is a marker for interstitial cells of Cajal (ICC). ICCs interact with enteric neurons and are essential for gastrointestinal motility. The roles of neural crest-derived cells, neurons, Kit, and Kit ligand (KL) in ICC development were analyzed. ICC development lagged behind that of neurons and smooth muscle. Although mRNA encoding Kit and KL was detected at E11, Kit-immunoreactive ICCs did not appear until E12 in foregut and E14 in terminal hindgut. Transcripts of Kit and KL and Kit-immunoreactive cells were found in aganglionic gut from ls/ls and c-ret -/- mice. ICCs also developed in crest-free cultures of ls/ls terminal colon. ICCs appeared in cultures of noncrest- but not those of crest-derived cells isolated from the fetal bowel by immunoselection with antibodies to p75(NTR). KL immunoreactivity was coincident in cells with neuronal or smooth muscle markers. The development of ICCs in cultures of mixed cells dissociated from the fetal gut was dependent on plating density. No ICCs appeared at </=80,000 cells/ml, but many cells, including filamentous ICCs, appeared at >/=200,000 cells/ml. Exogenous KL partially substituted for a high plating density. These data support the ideas that mammalian ICCs are neither derived from the neural crest nor developmentally dependent on neurons. ICC differentiation/survival requires KL, which can be provided by neurons or cells in a smooth muscle lineage. Neurons may be needed for development of myenteric ICCs and the mature ICC network.

Animals↗

PubMed1998

Evaluation of the effect of food on the pharmacokinetics of avitriptan.

Bioavailability of avitriptan was found to decrease significantly when administered 5 min after a standard high fat meal. The studies described herein were carried out to gain insight into the mechanism of this food effect. A series of studies were conducted in humans to assess the effect of timing of meal, type of meal, gastric pH, change in the formulation and dose on the bioavailability of avitriptan. Avitriptan was administered as a 50 mg capsule under fasted condition and at 30 min, 1, 2 and 4 h after a standard high fat meal. The reduction in avitriptan bioavailability persisted even at 4 h post high fat meal, although as the time interval between the meal and dose increased, the effect of meal tended to decrease. Bioavailability of avitriptan also decreased significantly when the drug was administered after a high protein and a high carbohydrate meal. Elevation in gastric pH caused by food was not found to be responsible for the food-related decrease in bioavailability of avitriptan since ranitidine pretreatment did not lead to a decrease in bioavailability. When administered as a 50 mg 14C-labeled solution after a standard high fat meal, bioavailability of avitriptan decreased although the decrease was less compared with that observed for a capsule dosage form. Plasma concentrations and cumulative urinary excretion of total radioactivity also decreased in the fed condition, indicating the absorption of avitriptan was affected. The decrease in avitriptan AUC was somewhat more pronounced than the decrease in the exposure to the total radioactivity suggesting a food-related increase in the first-pass metabolism of avitriptan. Effect of the standard high fat meal on avitriptan administered as a 150 mg capsule was similar to that observed at the 50 mg dose. Overall, the results indicate that bioavailability of avitriptan is significantly reduced irrespective of the type of meal, dose and dosage form and the effect persists for as long as 4 h post meal. Thus, it appears that avitriptan absorption and bioavailability are highly sensitive to presence of food in the stomach and any food-related changes in gastric emptying time and gastrointestinal motility.

Area Under Curve↗

PubMed1999

Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine.

Plants from all over the world such as Eleutherococcus senticosus, Panax ginseng, Raponticum carthamoides, Rhodiola rosea, Withania somnifera and Ocimum sanctum have been extensively evaluated for their adaptogenic potential. However, none of them has been successfully introduced as an adaptogen in the clinic. This paper discusses some of the problems in evaluation of adaptogens which have precluded their inclusion as clinically useful drugs. We further discuss our results with six rasayana plants from Ayurveda, which were studied for their adaptogenic potential. The whole, aqueous, standardized extracts of selected plants (Tinospora cordifolia, Asparagus racemosus, Emblica officinalis, Withania somnifera, Piper longum and Terminalia chebula) were administered orally to experimental animals, in a dose extrapolated from the human dose, following which they were exposed to a variety of biological, physical and chemical stressors. These plants were found to offer protection against these stressors, as judged by using markers of stress responses and objective parameters for stress manifestations. Using a model of cisplatin induced alterations in gastrointestinal motility, the ability of these plants to exert a normalizing effect, irrespective of direction of pathological change was tested. All the plants reversed the effects of cisplatin on gastric emptying, while Tinospora cordifolia and Asparagus racemosus also normalized cisplatin induced intestinal hypermotility. Tinospora cordifolia was also tested for its ability to modulate the changes occurring in the phagocytic activity of peritoneal macrophages after exposure of rats to either carbon tetrachloride or horse serum. It was found to normalize the phagocytic function irrespective to the direction of change, complying to the definition of an adaptogen. All the plant drugs were found to be safe in both acute and subacute toxicity studies. Studies on the mechanisms of action of the plants revealed that they all produced immunostimulation. The protection offered by Tinospora cordifolia against stress induced gastric mucosal damage was lost if macrophage activity was blocked. Emblica officinalis strengthened the defence mechanisms against free radical damage induced during stress. The effect of Emblica officinalis appeared to depend on the ability of target tissues to synthesize prostaglandins. Recent data obtained with Tinospora cordifolia suggest that it may induce genotypic adaptation, further opening the arena for more research and experimentation.

Adaptation, Physiological↗

PubMed1977

Postganglionic cholinergic dysautonomia.

A 9-year-old boy presented with symptoms and signs of marked postganglionic cholinergic autonomic dysfunction manifested by bilateral internal ophthalmoplegia, impaired secretion of tears and saliva, lack of gastrointestinal motility, atony of the bladder, generalized absence of sweating, and hypertension. Clinical and pharmacological studies confirmed that the abnormalities were restricted mainly to the postganglionic cholinergic autonomic system and showed evidence of postdenervation supersensitivity to parasympathomimetic drugs. The patient was treated in the early phase of his illness by the administration of carbachol, and eventually he made a slow and partial spontaneous recovery. Histoimmunofluorescent studies on a skin biopsy specimen suggested an autoimmune origin for his disease, with IgG antibodies being produced against postganglionic cholinergic autonomic fibers.

Autoimmune Diseases↗

PubMed1995

Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals.

In addition to metabolic differences, the anatomical, physiological, and biochemical differences in the gastrointestinal (G.I.) tract of the human and common laboratory animals can cause significant variation in drug absorption from the oral route. Among the physiological factors, pH, bile, pancreatic juice, and mucus and fluid volume and content can modify dissolution rates, solubility, transit times, and membrane transport of drug molecules. The microbial content of the G.I. tract can significantly affect the reductive metabolism and enterohepatic circulation of drugs and colonic delivery of formulations. The transit time of dosage forms can be significantly different between species due to different dimensions and propulsive activities of the G.I. tract. The lipid/protein composition of the enterocyte membrane along the G.I. tract can alter binding and passive, active, and carrier-mediated transport of drugs. The location and number of Peyer's patches can also be important in the absorption of large molecules and particulate matter. While small animals, rats, mice, guinea pigs, and rabbits, are most suitable for determining the mechanism of drug absorption and bioavailability values from powder or solution formulations, larger animals, dogs, pigs, and monkeys, are used to assess absorption from formulations. The understanding of physiological, anatomical, and biochemical differences between the G.I. tracts of different animal species can lead to the selection of the correct animal model to mimic the bioavailability of compounds in the human. This article reviews the anatomical, physiological, and biochemical differences between the G.I. tracts of humans and commonly used laboratory animals.

Animals↗

PubMed1989

Clinical results of colectomy for severe constipation.

Subtotal colectomy has been performed in 40 patients with severe constipation. Only one patient was male. Five patients (13 per cent) had a history of a serious psychiatric disorder. Twenty-six patients (65 per cent) could not expel a 100-ml air-filled balloon and 19 patients (48 per cent) had electromyographic evidence of abnormal puborectalis contraction during attempted defaecation before operation. Median preoperative passage of 50 radio-opaque markers over 5 days was 16 per cent. Sixteen patients had had a previous anorectal myectomy to exclude Hirschsprung's disease. Initial resections were subtotal colectomy and ileorectal anastomosis (n = 34), caecorectal (n = 5) or ileosigmoid (n = 1) anastomosis. Secondary operations included restorative proctocolectomy and ileal pouch-anal anastomosis (n = 6) and six patients eventually had an ileostomy. Median bowel frequency per week significantly increased after operation (0.3 (range 0-1) preoperatively to 21 (range 2-70) postoperatively, P less than 0.005), the percentage of patients with abdominal pain fell after operation from 93 to 39 per cent but symptoms of abdominal distension remained the same (86 per cent preoperatively and 82 per cent postoperatively).

Adult↗

PubMed2005

Validation and application of a high-performance liquid chromatography--tandem mass spectrometry assay for mosapride in human plasma.

A simple, rapid, sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of mosapride (I), a novel and potent gastroprokinetic agent that enhances the upper gastrointestinal motility by stimulating 5-HT(4) receptor. The analyte and internal standard, tamsulosin (II), were extracted by liquid-liquid extraction with diethyl ether-dichloromethane (70:30, v/v) using a Glas-Col Multi-Pulse Vortexer. The chromatographic separation was performed on a reversed-phase Waters symmetry C(18) column with a mobile phase of 0.03% formic acid-acetonitrile (10:90, v/v). The protonated analyte was quantitated in positive ionization by multiple reaction monitoring with a mass spectrometer. The mass transitions m/z 422.3 -->198.3 and m/z 409.1 -->228.1 were used to measure I and II, respectively. The assay exhibited a linear dynamic range of 0.5-100.0 ng/mL for mosapride in human plasma. The lower limit of quantitation was 500 pg/mL with a relative standard deviation of less than 15%. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. A run time of 2.0 min for each sample made it possible to analyze a throughput of more than 400 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability or bioequivalence studies.

Benzamides↗

PubMed2002

Localisation of cannabinoid CB(1) receptor immunoreactivity in the guinea pig and rat myenteric plexus.

Activation of cannabinoid CB(1) receptors inhibits gastrointestinal motility, propulsion, and transit, whereas selective antagonism of these receptors has the opposite effects, suggesting the presence of endocannabinoid tone. Supporting evidence for presynaptic CB(1) receptors on myenteric neurons has been found in vitro. In this study, selective CB(1) receptor antibodies and neuronal markers were used to identify and characterise myenteric neurons expressing cannabinoid receptors. Whole mounts of rat and guinea pig myenteric preparations were dually labelled with antibodies against the CB(1) receptor and choline acetyltransferase, neurofilament proteins, calbindin, calretinin, synapsin I, microtubule-associated protein-2, calcitonin gene-related peptide, or substance P. The pattern of CB(1) receptor labelling and the neurochemical classification of CB(1) receptor-positive cells were markedly influenced by the species and fixation procedure. Virtually all choline acetyltransferase-immunoreactive myenteric neurons expressed CB(1) receptors in ganglia from both species. Subpopulations of neurons identified with calbindin, calretinin, and microtubule-associated protein-2 did not express CB(1) receptors. A few calcitonin gene-related peptide- and substance P-positive somata coexpressed CB(1) receptor immunoreactivity but showed little colocalisation on individual fibres. There was a close association between CB(1) receptor immunoreactivity and fibres labelled for synaptic protein, suggesting a role in the modulation of transmitter release. Functional responses to cannabinoids in the presence of hexamethonium suggest further that CB(1) receptors occur on excitatory motoneurons. In conclusion, CB(1) receptors are expressed on a variety of cholinergic sensory, interneuronal, and motor neurons in myenteric ganglia.

Animals↗

PubMed2002

Distribution of galanin receptor 1 immunoreactivity in the rat stomach and small intestine.

Galanin affects gastrointestinal functions by activating different G protein-coupled receptors. Here, we identified the sites of expression of the galanin receptor 1 (GAL-R1) subtype in the rat stomach and small intestine by using immunohistochemistry with an antibody raised to the third intracellular loop of rat GAL-R1 (GAL-R1(Y225-238)) and confocal microscopy. Antibody specificity was confirmed by (1) the detection of a band at approximately 70 kDa in Western blot of membranes from GAL-R1 transfected cells, (2) the cell surface staining of GAL-R1 transfected cells, which was not detected in control cells, and (3) the abolition of Western signal and tissue immunostaining by preadsorbing the antibody with the peptide used for immunization. GAL-R1 immunoreactivity was localized to the cell surface of enterochromaffin-like cells, and of myenteric and submucous neurons, and to fibers distributed to the plexuses, interconnecting strands, muscle layers, vasculature, and mucosa. A dense network of GAL-R1 immunoreactivity was observed in the deep muscular plexus in very close association with interstitial cells of Cajal visualized by c-kit immunostaining. In the ileum, 81.6% of GAL-R1 myenteric neurons and 70.7% of GAL-R1 submucosal neurons were substance P immunoreactive. Vasoactive intestinal polypeptide immunoreactivity was found in 48.3% of GAL-R1 submucosal neurons, but not in GAL-R1 myenteric neurons. These findings support the hypothesis that GAL-R1 mediates galanin actions on gastrointestinal motility and secretion by modulating the release of other neurotransmitters and contributes to galanin-induced inhibition of gastric acid secretion by means of the suppression of endogenous histamine release.

Animals↗

PubMedDate not supplied

Therapy of type 2 diabetes mellitus based on the actions of glucagon-like peptide-1.

GLP-1 is a peptide hormone from the intestinal mucosa. It is secreted in response to meal ingestion and normally functions in the so-called ileal brake, that is, inhibition of upper gastrointestinal motility and secretion when nutrients are present in the distal small intestine. It also induces satiety and promotes tissue deposition of ingested glucose by stimulating insulin secretion. Thus, it is an essential incretin hormone. In addition, the hormone has been demonstrated to promote insulin biosynthesis and insulin gene expression and to have trophic effects on the beta cells. The trophic effects include proliferation of existing beta cells, maturation of new cells from duct progenitor cells and inhibition of apoptosis. Furthermore, glucagon secretion is inhibited. Because of these effects, the hormone effectively improves metabolism in patients with type 2 diabetes mellitus. Thus, continuous subcutaneous administration of the peptide for six weeks in patients with rather advanced disease greatly improved glucose profiles and lowered body weight, haemoglobin A(1C), and free fatty acids (FFA). In addition, insulin sensitivity doubled and insulin responses to glucose were greatly improved. There were no side effects. Continuous administration is necessary because of rapid degradation by the enzyme dipeptidyl peptidase-IV. Alternative approaches include the use of analogues that are resistant to the actions of the enzyme, as well as inhibitors of the enzyme. Both approaches have shown remarkable efficacy in both experimental and clinical studies. The GLP-1-based therapy of type 2 diabetes, therefore, represents a new and attractive alternative.

Appetite Regulation↗

PubMed2007

Kit signaling is essential for development and maintenance of interstitial cells of Cajal and electrical rhythmicity in the embryonic gastrointestinal tract.

Interstitial cells of Cajal (ICC) are specialized cells in smooth muscle organs that generate and propagate pacemaker activity, receive inputs from motor neurons, and serve as mechanosensors. In the gastrointestinal tract, development and maintenance of the ICC phenotype have been linked to intracellular signaling via Kit, but its role in development of ICC during embryogenesis is controversial. Here we have studied the development of functional ICC-MY during the late gestational period in mice. Blocking Kit with a neutralizing antibody before and after development of spontaneous electrical activity (E17 to P0) caused loss of ICC-MY networks and pacemaker activity. ICC-MY and pacemaker activity developed normally in W/+ and W(V)/+ heterozygotes, but failed to develop between E17 to P0 in W/W(V) embryos with compromised Kit function. Muscles treated with Kit neutralizing antibody or the tyrosine kinase inhibitor, imatinib mesylate (STI571), from E17-P0 for 3 days caused loss of functionally developed ICC-MY networks, but ICC-MY and pacemaker activity recovered within 9 days after discontinuing treatment with neutralizing antibody or imatinib mesylate. These data suggest that Kit signaling is an important factor in lineage decision and in the development of functional ICC in late gestation. ICC-MY demonstrate significant plasticity in gastrointestinal tissues. Manipulation of the ICC phenotype might provide useful therapies in gastrointestinal disease where the Kit-positive cell population is either lost or amplified.

Animals↗

PubMed1987

Jejunal ulceration and stricture due to wax-matrix potassium chloride tablets and amitriptyline.

A 68-year-old woman presented with abdominal distention of several weeks duration and an acute small bowel obstruction. For several years she had been prescribed amitriptyline 150 mg/d, L-thyroxine 100 micrograms/d, and digoxin 0.25 mg/d. For the previous year she had been taking hydrochlorothiazide 50 mg/d and wax-matrix KCl 20 mEq/d for hypertension. At surgery a "napkin-ring" stricture of the midjejunum was found. It had microscopic features consistent with KCl local toxicity. It is speculated that delayed gastrointestinal motility secondary to amitriptyline predisposed this patient to wax-matrix KCl toxicity and that this potential side effect be considered when prescribing wax-matrix KCl.

Aged↗

PubMed1989

Parathyroid hormone-related protein relaxes rat gastric smooth muscle and shows cross-desensitization with parathyroid hormone.

Previously, we reported that parathyroid hormone (PTH) is a potent and effective relaxant of rat gastrointestinal smooth muscle. Since the recently discovered PTH-related protein (PTHrP) has amino-terminal homology with PTH and acts like PTH on bone and kidney, we decided to study the effects of synthetic PTHrP analogs on the isometric tension of rat fundic strips. Rat (r) PTH-(1-34), human (h) PTHrP-(1-34), and [Tyr0]hPTHrP-(1-34) relaxed acetylcholine-stimulated fundic strips in a dose-dependent manner, with an IC50 of 6, 10, and 31 nM, respectively. However, maximal doses of [Tyr0]hPTHrP-(1-34) were considerably less effective than the other two peptides. Addition of rPTH-(1-34) or hPTHrP-(1-34) to a maximally effective dose of [Tyr0]hPTHrP-(1-34) produced no further relaxation, indicating that [Tyr0]hPTHrP-(1-34) also has antagonistic properties. Bovine PTH-(3-34) an established in vitro antagonist of PTH, partially inhibited the relaxant effect of PTHrP. Fundic strips that had been desensitized by preincubation for 30-45 minutes with either rPTH-(1-34) or hPTHrP-(1-34) (330-500 nM) were also insensitive to the relaxant action of either peptide, but in the same preparations, the relaxation produced by vasoactive intestinal peptide was unaffected. These studies indicate that PTHrP and PTH can interact with the same receptor. Whether PTHrP influences gastrointestinal motility in normal or tumor-bearing persons remains to be investigated.

Animals↗

PubMed2004

Why are taeniae, haustra, and semilunar folds differentiated in the gastrointestinal tract of mammals, including man?

When a small change, either contraction or dilation, of the surface area of a digestive tube coincides with a considerable change in internal volume, this can be considered an effective influence of surface on volume. This study discusses the effects of anatomical differences between those types of digestive tracts where the longitudinal musculature is reduced to small bands, the taeniae, and those where such differentiations are not found. With the help of a geometric model the efficiency of transport (eta = net volume expelled aborally / volume of the tube) from haustra in tubes with two, three, four, and six taeniae was determined. It could be shown that efficiency of transport from haustra decreases when the number of taeniae increases. The second model applies the program "Surface Evolver" (author K.A. Brakke). The program is applied to investigate the relationships between changes in surface area of tubes with different numbers of taeniae (0, 2, 3, 4, and 6) and the respective changes of the internal volumes of tubes. Both haustra formation and formation of semilunar folds between haustra are considered. Tubes with two or three taeniae reduce their internal volume more efficiently than all others, namely, with a relatively small reduction of the surface area and contraction of the Tunica muscularis at a relatively low rate. In addition to chemical and mechanical decomposition of digesta the gastrointestinal tube has three tasks: propagation, storage, and retention of digesta. A tube without taeniae, i.e., with a complete longitudinal muscular layer, propagates contents with peristaltic movements. Storage can take place in areas of the tract with a dilated cross-section. Finally, folds can retain digesta. In many sections of the gastrointestinal tract folds are differentiated as permanent structures. However, folds formed with relatively little contraction of the musculature, i.e., little change in the surface area, represent an effective means of retention and thus of flow regulation. Tubes with taeniae and semilunar folds are adaptations for this effective type of regulation of digesta transit through the tract.

Animals↗

PubMed1995

Anti-nutritional factors of Datura in feedstuffs.

Soybean seed, linseed, some cereals seeds, and their by-products are infected by Datura seed weed of different varieties. The most common Datura spp. noxious to the farm animals are D. stramonium (atropine alkaloid) and D. ferox (scopolamine, 98-100% of total alkaloids) mainly present in Europe and South America, respectively. The presence of alkaloids from Datura seeds in feedingstuffs may be responsible for chronic and/or subclinical toxic effects; acute poisoning from Datura seeds are rare. Pigs are the most sensitive animals to Datura poisoning, followed by cattle, horses, and chickens. Sheep and rabbits are indifferent to atropine presence in food because they synthesize the atropine esterase enzyme. The progressive atropine poisoning in pigs leads to a reduction of feed intake and growth, gastrointestinal motility and secretory activity, extreme mouth dryness, increased respiration and cardiac rate, pupil dilation, etc. Clinical symptoms are partly similar among different species. Toxic effects from Datura alkaloids presence in feeds showed possible variability of alkaloids content tolerated by pigs. In our recent trials, the threshold limit in pigs (20-60 kg live weight) was 1.5 mg alkaloids/kg of feed (1.21 mg alkaloids/kg l.w.75).

Alkaloids↗

PubMed1997

Diabetic rats prefer glucose-paired flavors over fructose-paired flavors.

Prior studies indicate that glucose has a more potent postingestive reinforcing effect than fructose. The role of insulin in this effect was examined by comparing sugar-conditioned flavor preferences in normal and streptozotocin-diabetic rats. In Experiment 1, diabetic rats, like normal rats, preferred a cue flavor that had been mixed into 8% glucose solution over a flavor mixed with 8% fructose. Both taste and postingestive properties of glucose may have contributed to this preference. Experiment 2 evaluated postingestive reinforcement by pairing cue flavors with intragastric infusions of glucose and fructose. Both diabetics and normals acquired a preference for the flavor paired with intragastric 16% glucose infusions over the flavor paired with 16% fructose infusions although the preference was somewhat smaller in the diabetic rats. Taken together, the results indicate that a normal insulin secretory response to glucose is not required for glucose-conditioned flavor preference. The diabetic rats' reduced flavor preference in Experiment 2 suggests that insulin may play some role in glucose conditioning although this may be secondary to alterations in gastrointestinal motility characteristic of diabetic animals.

Animals↗

PubMed1993

Solution structure of casokefamide.

Casokefamide (Tyr-D-Ala-Phe-D-Ala-Tyr-NH2) is a synthetic peptide derived from the beta-casomorphin sequence, designed to increase the resistance to gastric proteases. Casokefamide binds to both mu and delta-opioid receptors, while beta-casomorphins and its fragments are typical mu-opioid receptor agonists. Furthermore, casokefamide can affect gastric acid and pancreatic exocrine secretions and also gastrointestinal motility. We have undertaken a conformational study on this peptide based on NMR measurements in a DMSOd6/H2O cryomixture at 265 K and energy calculations. The predominant conformation is characterised by the absence of regular structures and intramolecular hydrogen bonds. The conformation of the message domain is reminiscent of the shape of several peptidic and non peptidic opiates, with the D-Ala2CH3 group sandwiched between Tyr1 and Phe3 aromatic rings.

Amino Acid Sequence↗

PubMed1997

Acute experimental distal colitis alters colonic transit in rats.

Data from humans with active distal colitis suggest that the proximal colon exhibits increased contractile activity and delayed transit, whereas the distal colon shows decreased contractile activity and rapid transit. The present study used the acetic acid rat model of experimental colitis to determine the effect of distal colitis on total and regional colonic transit in vivo and on the in vitro contractility of circular smooth muscle from the proximal and distal colon. Distal colitis was induced in rats by intracolonic administration of 4% acetic acid; sham control rats received saline enemas. Control and colitic rats were studied 2 days postenemas. Total colon transit was determined by calculating the geometric center of distribution of a radiolabeled marker (51Cr) instilled into the proximal colon. Regional transit was assessed by expressing the radioactivity in the cecum, proximal and distal colon, and excreted stool as a percent of total radioactivity. Muscle strips from the proximal and distal colon were stimulated with 100 microM acetylcholine (ACh) and 60 mM KCl and the tension was expressed as kilograms per square centimeter. Distal colitis was characterized by decreased total colon transit, increased retention of marker in the cecum and proximal colon, and decreased retention of marker in the distal colon. In vitro contractility studies revealed that distal colitis increased proximal colon circular smooth muscle contractility and decreased distal colon circular smooth muscle contractility to both ACh and potassium. Distal colitis is associated with regional differences in colonic circular smooth muscle contractility, which may contribute to delayed transit in the proximal colon and rapid transit in the distal colon.

Acetylcholine↗