Regions Of Small Intestine Research Articles

Improvement of absorption enhancing effects of n-dodecyl-β-d-maltopyranoside by its colon-specific delivery using chitosan capsules

In general, absorption enhancing effects of various absorption enhancers were greater in the large intestine than those in the small intestinal regions. Therefore, the effectiveness of absorption enhancers is expected to be remarkably observed, if these enhancers can be delivered to the large intestine with some poorly absorbable drugs after oral administration. In this study, therefore, we examined whether chitosan capsules were effective for the colon-specific delivery of a certain absorption enhancer and can improve the absorption enhancing action of the absorption enhancer after oral administration. 5(6)-Carboxyfluorescein (CF) was used as a model drug to investigate the site-dependent effectiveness of various absorption enhancers by an in situ closed loop method. Sodium glycocholate (NaGC), n-dodecyl-beta-d-maltopyranoside (LM), sodium salicylate (NaSal) and sodium caprate (NaCap) were used as models of absorption enhancers in this study. Overall, the absorption enhancing effects of these enhancers for intestinal absorption of CF were greater in the colon than those in the jejunum and the ileum. Especially, among these enhancers tested in this study, LM showed much greater absorption enhancing effect in the colon than in the jejunum and the ileum. Therefore, LM was selected as a model absorption enhancer to examine the effect of chitosan capsules on the absorption enhancing effect of LM. When CF and LM were orally administered to rats using chitosan capsules, the plasma concentration of CF was much higher than those in other dosage forms including solution and gelatin capsules. Therefore, chitosan capsules may be useful carriers for colon-specific delivery of LM, thereby increasing its absorption enhancing effect from the intestinal membranes.

Immunohistochemical Characterization of the Distribution of Galectin-4 in Porcine Small Intestine

Galectins are an evolutionarily conserved family of 15 different lectins found in various combinations in virtually every type of animal cell. One of the primary galectins expressed in intestinal epithelium is galectin-4, a tandem-repeat galectin with two carbohydrate-recognition domains in a single polypeptide chain. In the current study, we produced an anti-galectin-4 monoclonal antibody (MAb) for determining the distribution of galectin-4 in porcine small intestine to enhance our understanding of where galectin-4 performs its functions in the small intestine. In immunohistochemistry studies, this MAb detected galectin-4 primarily in the cytoplasm of absorptive epithelial cells lining intestinal villi. Mature epithelial cells at the villous tips stained the most intensely with this MAb, with progressively less intense staining observed along the sides of villi and into the crypts. In addition to its cytoplasmic localization, galectin-4 was also associated with nuclei in villous tip cells, indicating that some galectin-4 may migrate to the nucleus during terminal maturation of these cells. In intestinal crypts, a specific subset of cells, which may be enteroendocrine cells, expressed galectin-4 at a relatively high level. Galectin-4 distribution patterns were similar in all three regions (duodenum, jejunum, and ileum) of porcine small intestine.

Changes in Carboxypeptidase A, Dipeptidase and Na+/K+ ATPase Activities in the Intestine of Rats Orally Exposed to Different Doses of Cadmium

The purpose of the present study was to evaluate the effect of cadmium on some protein digestive and absorption enzymes in rats. Thirty-six rats were grouped into three groups of 12 animals each; one group received deionised water and acted as control. One group received 445 microM Cd and the last group received 890 microM Cd in their drinking water for a period of one month. The results obtained indicate that increasing the level of cadmium from 445 microM to 890 microM in the drinking water of the rats led to 29% and 23% increase in accumulated cadmium in the proximal and distal small intestine respectively. The body weight gain of rats exposed to 445 microM and 890 microM Cd was decreased by about 24% and 43% respectively when compared with the control. The activities of carboxypeptidase A, dipeptidase and Na+/K+ ATPase were reduced in the mucosa of the proximal end of the small intestine of cadmium exposed rats. The reduction was dose dependent; with the 890 microM Cd exposed rats displaying the least activities. In the distal small intestine, the activities of these enzymes were restored in the 445 microM Cd exposed rats to levels that were not statistically different (P > 0.05) from those observed in the controls. In the 890 microM Cd exposed rats, dipeptidase activity improved by about 80% compared with the activity of the enzyme in the proximal small intestine. Likewise, Na+/K+ ATPase activity increased by about 125% compared with the observed level in the proximal small intestine. The study suggests that cadmium given to rats in drinking water compromise protein digestion and absorption of nutrients particularly in the proximal region of small intestine and could account for weight reduction associated with cadmium toxicity.

Absorption of α-ketoglutarate by the gastrointestinal tract of pigs

Only a small percentage of α-ketoglutarate (AKG) administered lumenally to pigs appears in the portal circulation. This has been attributed to mucosal metabolism, and possibly by limited absorption. Although transporters for di- and tricarboxylic acids, which includes the sodium-dependent transporter NaDC-1, have been detected in the small intestine, correlations with functional assays are lacking. Therefore, intact tissues from three regions of the small intestine, stomach, and colon of weaned pigs were used to measure rates of AKG absorption. Western analysis was used to detect NaDC-1 in the three regions of small intestine. Rates of AKG absorption were highest in the small intestine, lowest in the colon, and intermediate in the stomach. Immunoreactive NaDC-1 was detected in the small intestine and this coincided with a component of AKG absorption that was inhibited by AKG and succinate. In contrast, absorption of AKG was inhibitable by unlabeled AKG, but not succinate, in the stomach, and by neither in the colon. Feeding studies indicated that the amounts of AKG that might be included in practical diets for pigs would not (1) upregulate rates of AKG absorption or (2) exceed estimated capacities of the small intestine to absorb AKG. The present findings indicate that the efficacy of AKG as an alternative metabolic fuel for enterocytes to spare dietary amino acids is not limited by absorption.

In-vitro and In-vivo Evaluation of Mesalazine–Guar Gum Matrix Tablets for Colonic Drug Delivery

The aim of this study was to develop colon-specific delivery systems for mesalazine (5-ASA) using guar gum as a carrier. A colon specific matrix tablet of mesalazine with guar gum was evaluated by in vitro and in vivo X-ray studies in humans. Two different types of guar gum were used in the experiments. Tablets were prepared by the slugging method. The physical properties of tablets were tested and in vitro release studies were performed by a flow-through cell apparatus with and without galactomannanase enzyme. The type and the amount of guar gum affected the in vitro release of drug from the matrix tablets. High viscosity guar gum, in the form of a matrix tablet was capable of protecting the drug from being released in the upper region of gastrointestinal (GI) system, i.e. stomach and small intestine. X-ray imaging technique was used to monitor the tablets throughout the GI system on 8 healthy volunteers. Barium sulphate was used as a marker in the tablets for in vivo studies. These results showed that, the matrix tablets reached the colon; not being subjected to disintegration in the upper region of the GI system in all the subjects.

Na+/glucose co-transporter abundance and activity in the small intestine of lambs: enhancement by abomasal infusion of casein

The purpose of the present study was to determine the effect of abomasal casein infusion on glucose uptake and abundance of the Na+/glucose co-transporter (SGLT1) 1 in the ovine small intestine. Lambs (body weight 35 (sem 1.0) kg) were surgically fitted with abomasal infusion catheters and were fed diets containing equal portions of wheat hay and cracked maize. Lambs were infused with either 500 g water/d or with 500 g water containing 35 g casein/d. The infusion period lasted 10 d, after which lambs were killed, exsanguinated and eviscerated. Brush border membrane vesicles (BBMV) were prepared using mucosa from different small intestinal regions. Intake and total tract digestibility of nutrients were similar between treatments and averaged 1134, 1142 and 486 g/d and 67, 70, and 94 % for DM, organic matter and non-structural carbohydrates respectively. Crude protein (Nx6.25) digestibility was 15 % greater in the casein-infused than control lambs. Glucose uptake to BBMV ranged from 101 to 337 pmol/mg protein per s along the small intestine and was greatest in the mid-section of the small intestine. In the mid-jejunum, glucose uptake was greater (P<0.07) in lambs infused with casein and averaged 120 pmol/mg protein per s compared with 68 pmol/mg protein per s in the control group. SGLT1 affinity was similar between treatments and averaged 104 microm in the different segments of the small intestine of lambs. However, lambs infused with casein exhibited similar values along the small intestine and affinity averaged 106 microm, while in the control group a greater affinity (85 microm) was measured in the mid-jejunum. SGLT1 protein abundance was correlated with glucose uptake in the BBMV in the casein-treated lambs, but not in the control group. These results suggest that glucose uptake along the small intestine of lambs is influenced by casein or its derivatives in the small intestine via SGLT1 affinity and activity at the brush border membrane, and that SGLT1 activity may be regulated by post-translational events affected by amino acids and peptides.

Keratin 20 helps maintain intermediate filament organization in intestinal epithelia.

Of the >20 epithelial keratins, keratin 20 (K20) has an unusual distribution and is poorly studied. We began to address K20 function, by expressing human wild-type and Arg80-->His (R80H) genomic (18 kb) and cDNA K20 in cells and mice. Arg80 of K20 is conserved in most keratins, and its mutation in epidermal keratins causes several skin diseases. R80H but not wild-type K20 generates disrupted keratin filaments in transfected cells. Transgenic mice that overexpress K20 R80H have collapsed filaments in small intestinal villus regions, when expressed at moderate levels, whereas wild-type K20-overexpressing mice have normal keratin networks. Overexpressed K20 maintains its normal distribution in several tissues, but not in the pancreas and stomach, without causing any tissue abnormalities. Hence, K20 pancreatic and gastric expression is regulated outside the 18-kb region. Cross-breeding of wild-type or R80H K20 mice with mice that overexpress wild-type K18 or K18 that is mutated at the conserved K20 Arg80-equivalent residue show that K20 plays an additive and compensatory role with K18 in maintaining keratin filament organization in the intestine. Our data suggest the presence of unique regulatory domains for pancreatic and gastric K20 expression and support a significant role for K20 in maintaining keratin filaments in intestinal epithelia.

Gastrointestinal stromal tumor: involvement in urologic patients and recent therapeutic advances

Gastrointestinal stromal tumor (GIST) is a recently described mesenchymal cancer that can arise from any portion of the GI tract, most commonly from the stomach (39%), small intestine (32%), and colorectal regions (15%) (1). These tumors, which were often previously classified as leiomyomas or leiomyosarcomas, can invade the urinary tract, and patients with GIST can develop urologic cancers or other urologic conditions. Urologists should therefore be cognizant of the recent advances in the treatment of GIST with imatinib mesylate (also known as Gleevec or STI571), because they can directly influence patient treatment and prognosis. In addition, the development of this targeted molecular therapeutic agent provides a glimpse into the future of oncology.

A stereologic evaluation of glucagon-like peptide-1 (GLP-1) mucosal cells in the small intestine of the developing pig.

Studies that investigate possible developmental changes in gastrointestinal hormones in the pig are sparse and contradictory. Therefore, a quantitative morphological study using stereologic methods on paraffin sections of the different small intestinal regions (cranial and caudal duodenum, jejunum and ileum) of the developing pig (second half of the gestation, neonatal and weaning period) has been conducted. The sections were processed for GLP-1-immunohistochemistry. During the investigated time span, the volume of GLP-1-IR cells increased approximately 40-fold in both the jejunum and ileum, notwithstanding a decrease of their volume density. The ileal small intestinal segment contained the highest volume density of GLP-1-IR cells. In contrast, GLP-1-IR cells were only occasionally encountered in the duodenum. The development-related changes of the investigated parameters coincide with dietary changes and the regional differences are in accordance with functional reports that point to GLP-1 as a gastrointestinal hormone that ediates the 'ileal brake' and stimulates glucose-dependent pancreatic insulin secretion.

Effect of Vilon and Epithalon on glucose and glycine absorption in various regions of small intestine in aged rats.

Vilon (Lys-Glu) and Epithalon (Ala-Glu-Asp-Gly) administered orally for 1 month improved transport characteristics of the small intestine in aged rats. Vilon enhanced passive glucose accumulation in the serous fluid in inverted sac made from the distal region of the small intestine, while Epithalon enhanced this process in the medial region. Vilon stimulated active glucose accumulation in the serous sac of the medial small intestine, Epithalon - in the proximal and distal small intestinal segments. Glycine absorption increased only in the proximal intestinal segment under the effect of Epithalon.

A Novel Alkaline Phosphatase-Based Isolation Method Allows Characterization of Intraepithelial Lymphocytes from Villi Tip and Crypt Regions of Murine Small Intestine

The isolation of intestinal intraepithelial lymphocytes (IEL) is a major prerequisite for the investigation of cellular and molecular cross-talk in the intestinal mucosa. Since intestinal epithelial cells exhibit distinct functional features at the villi tip and crypt levels, such differences could extend to IEL. We developed a mechanical procedure for isolation of IEL from these distinct epithelial sites to test our hypothesis. Cells isolated from the intestinal epithelium by sequential incubations under stirring were segregated based upon their alkaline phosphatase (AP) activity since villi tip and crypt fractions expressed high and low AP activity, respectively. IEL preparations obtained after a further purification step in Percoll gradient contained >90% Integrin αIELchain+, CD3+T cells, and no Ig+cells. Villi tip IEL preparations possessed increased numbers of low density IEL when compared to crypt IEL, suggesting that distinct IEL-epithelial cell interactions occur at the intestinal villi tip and crypt levels.

Changing intestinal connective tissue interactions alters homeobox gene expression in epithelial cells.

In segmented organs, homeobox genes are involved in axial patterning and cell identity. Much less is known about their role in non-segmented endoderm derivatives such as the digestive epithelium. Using a xenograft model of fetal intestinal anlagen implanted under the skin of nude mice, we have investigated whether the expression of five homeobox genes (HoxA-4, HoxA-9, HoxC-8, Cdx-1 and Cdx-2) is modified when intestinal epithelium undergoes normal development or displays heterodifferentiation in association with heterotopic mesenchyme. In homotypic associations of fetal endoderm and mesenchyme that recapitulate normal development, the overall pattern of homeobox gene expression was maintained: HoxA-9 and HoxC-8 were the highest in the colon and ileum, respectively, and HoxA-4 was expressed all along the intestine; Cdx-1 and Cdx-2 exhibited an increasing gradient of expression from small intestine to colon. Yet, grafting per se caused a faint upregulation of HoxA-9 and HoxC-8 in small intestinal regions in which these genes are not normally expressed, while the endoderm-mesenchyme dissociation-association step provoked a decay of Cdx-1 in the colon. In heterotopic associations of colonic endoderm with small intestinal mesenchyme, the colonic epithelium exhibited heterodifferentiation to a small intestinal-like phenotype. In this case, we observed a decay of HoxA-9 expression and an upregulation of HoxC-8. Additionally, heterodifferentiation of the colonic epithelium was accompanied by a downregulation of Cdx-1 and Cdx-2 to a level similar to that found in the normal small intestine. To demonstrate that mesenchyme-derived cells can influence Cdx-1 and Cdx-2 expression in the bowel epithelium, fetal jejunal endoderm was associated with intestinal fibroblastic cell lines that either support small intestinal-like or colonic-like morphogenesis. A lower expression of both homeobox genes was shown in grafts presenting the small intestinal phenotype than in those showing glandular colonic-like differentiation. Taken together, these results suggest that homeobox genes participate in the control of the positional information and/or cell differentiation in the intestinal epithelium. They also indicate that the level of Cdx-1 and Cdx-2 homeobox gene expression is influenced by epithelial-mesenchymal cell interactions in the intestinal mucosa.

Regional Expression and Dietary Regulation of Rat Small Intestinal Peptide and Amino Acid Transporter mRNAs

RT-PCR was used to obtain rat small intestinal cDNAs for two peptide transporters, showing conclusively for the first time that both are present in normal intestinal mucosa. Sequencing of these cDNAs showed them to be highly homologous and similar to two different types of peptide transport proteins from either colorectal carcinoma cells (Caco-2) or human and rabbit intestine. An even distribution profile of steady state levels of mRNA for both peptide transporters was observed along the longitudinal axis of small intestine. Both were upregulated in the distal regions of intestine by a high protein diet. Also, high levels of the rat high affinity glutamate transporter EAAC1 were observed in the distal intestine. These results suggest that the distal regions of small intestine play an important role in the absorption of some amino acids and peptides. Furthermore this area appears to be a primary site where dietary-induced changes in peptide and amino acid transport occurs.

Regional differences in motor responsiveness to antimuscarinic drugs in rabbit isolated small and large intestine

The pirenzepine-related analogue, nuvenzepine, and the antagonists selective for the three muscarinic receptor subtypes 4-DAMP (M, and M3 receptors), pirenzepine (M 1 receptors), methoctramine (M 2 receptors) have been tested on rabbit isolated small and large intestinal regions provided with spontaneous motor activity. The employed drugs differently affected intestinal motility patterns. The ileum pendular movements as well as the proximal colon and taenia coli tone, spike amplitude and frequency were concentration-dependently inhibited by the compounds here employed. Their pIC 50 values followed the rank order of potency generally reported for the involvement of the M 3 muscarinic receptors (4-DAMP≥atropine>nuvenzepine≥pirenzepine>methoctramine). Unlike nuvenzepine and the other antimuscarinics assayed, the M 1 selective antagonist pirenzepine, at nanomolar concentrations, was able to enhance the proximal taenia coli motility patterns suggesting that a M 1-inhibitory pathway might operate in the physiological modulation of taenia coli motility. At variance with longitudinal ileum and colon contractile activity, proximal circular colon motility was resistant to muscarinic as well as to α 1-, H 1-, 5-HT-blockade indicating that NANC neuronal mechanisms could act at this level. In summary, these data provide evidence that, at intestinal level, nuvenzepine is almost completely devoid of reliable M 1-linked effect thus possessing a different pharmacological selectivity at muscarinic receptor subtypes with respect to pirenzepine. Furthermore, it emerges that rabbit spontaneous small and large intestinal motility is probably driven by different physiological mechanisms regional-related. The peculiar circular colon refractoriness deserves further studies to be extended to the human tissue.

Effective Intestinal Absorption of Insulin in Diabetic Rats Using Enteric Coated Capsules Containing Sodium Salicylate

AbstractThe absorption of insulin manifested as percent reduction of blood glucose was evaluated after placement of capsules containing 4.6 units of the drug and 20 mg of Sodium salicylate as an absorption promoter in the rate stomach. The capsules were coated with either Eudragit L100 or Eudragit 9100 to deliver insulin in different regions of small intestine of the rats as they are pH dependent. The data obtained after administration of the capsules were compared with that after intraperitoneal injection of 1 U of insulin and ALSO after administration of coated capsules containing insulin alone. The administration of insulin capsules containing sodium salicylate result in a significant (p<0.01) increase of the hypoglycemic effect over the 5 h period of the experiments. They produced the same hypoglycemia effect as I.P. injection at 5 h point. The areas under the % blood glucose reduction curves produced were 363.5, 221.7 and 236.5% h for I.P. injection and capsules coated with Eudragit L100 and Eudragit...

Effect of age on gastrointestinal absorption of tobramycin in rats

Using newborn, suckling, weanling and adult rats, we studied the effect of age on the intestinal absorption of tobramycin, which is poorly absorbed in adult humans. The mean (±S.D.) bioavailability ( F) values after administering tobramycin (30 mg/kg) orally to newborn, suckling and weanling rats were 39.4 ± 5.8, 19.9 ± 4.6, and 2.8 ± 0.9%, respectively (significant differences). A marked difference was observed between suckling and weanling rats. After duodenal administration of tobramycin (30 mg/kg) to suckling rats, absorption occurred more readily than in adult rats ( F = 104.0 ± 33.6 vs 27.2 ± 5.7%), and the mean F values for both ages were significantly higher than those in the respective oral sham experiments. Therefore, a high concentration of tobramycin in the intestine promotes intestinal absorption. When the cumulative amounts of tobramycin transferred from the mucosal to serosal side were determined in suckling, weanling and adult rats by an everted sac method, the amount was highest for suckling rats, with an abrupt change being found between suckling and weanling rats. The permeation of tobramycin from the mucosal to serosal side was not a saturable process in rats of all ages. An aminoglycoside (AMG), neomycin (10 mM), and a polyamine, spermine (10 mM), significantly increased the permeating of tobramycin in the jejunum and ileum of suckling rats and the jejunum of adult rats. Choline chloride (10 mM), tetraethylammonium (10 mM) and 2,4-dinitrophenol (0.5 mM) did not affect the permeation of tobramycin in any small intestinal regions (jejunum and ileum) of either suckling or adult rats. The following conclusions were drawn: (1) tobramycin absorption occurs readily from the small intestine of suckling rats, but markedly decreases during the weaning period; (2) tobramycin is transferred predominantly via passive diffusion in the immature small intestine of suckling rats; and (3) the intestinal absorption of tobramycin can be enhanced by direct delivery of a high drug concentration exposed to the small intestine, and this absorption is further facilitated with other AMGs or polyamines in the small intestine, particularly in suckling rats.

Premicellar taurocholate enhances calcium uptake from all regions of rat small intestine

Background/Aims: The specific components of bile, which is necessary for normal calcium absorption, are unknown. We have previously shown that Ca2+ is bound with high affinity by premicellar taurocholate. The current studies examined the effects of taurocholate on intestinal calcium transport. Methods: Intestinal Ca2+ uptakes were measured from proximal, mid, and distal small intestinal segments perfused with solutions containing 45 CaCl2 (0.1–1 mmol/L), taurocholate (0–10 mmol/L), trihydroxymethylaminomethane buffer (pH 7), phenolsulfonpthalein (nonabsorbable marker), and NaCl (total ionic strength, 0.16 mol/L) for four randomized perfusion periods. In other studies, the proximal small intestine was divided into two equal segments and perfused with either 45CaCl2 or 45CaCl2 plus taurocholate (2.5–5 mmol/L). Calcium absorption was measured from the difference in uptake and calcium concentration retained in mucosa. Finally, effects of taurocholate on Ca2+ uptake across isolated brush border membrane vesicles were measured. Results: Premicellar taurocholate produced an approximately 1.7–2-fold enhancement (P < 0.01) in Ca2+ uptake in all regions, with lesser contributions from micellar taurocholate. These effects resulted in a net increase in calcium absorption. Premicellar taurocholate also significantly increased calcium uptake across brush border vesicles. Conclusions: Premicellar taurocholate significantly enhances calcium uptake into, and absorption across, enterocytes. The mechanisms remain to be experimentally verified.

Characterization of calcium-independent cytosolic phospholipase A2 activity in the submucosal regions of rat stomach and small intestine.

This study was undertaken to compare the calcium-independent phospholipase A2 (PLA2) activities in the cytosols of twelve rat tissues and to determine whether their activities were distinct. 1-O-Alk-1'-enyl-2-[14C]-oleoyl-sn-glycero-3-phosphocholine (PlsC) and 1-O-Alk-1'-enyl-2-[14C]oleoyl-sn-glycero-3-phosphoethanolamine (PlsE) were synthesized and used as substrates, instead of phosphatidyl compounds, to exclude hydrolysis by cytosolic PLA1 activity that could be present in some of the cytosolic preparations. For each tissue, we examined substrate specificity, pH optimum, and effect of adenosine triphosphate (ATP) and ATP analogues. PLA2 activity was detected in eleven out of the twelve issues examined. Based on substrate specificity and pH optimum, cytosolic calcium-independent PLA2 were classified in three groups. The first group, which included PLA2 from small intestine, stomach and spleen, had the highest specific activity with PlsC as substrate (1253, 309 and 75 nmol/mg protein/hour, respectively) and an optimal pH at 6.5. Activity with PlsE as substrate was much lower (20-37%) than with PlsC. The second group of PLA2 activities included the cytosolic activities from thymus, lung, liver and pancreas that showed lower specific activities for both substrates (14-23 nmol/mg protein/hour with PlsC) and had a broader optimal pH range of 6.1 to 7.5. The cytosols from brain, kidney, heart and muscle comprised the third PLA2 group that was found to have a higher specific activity with PlsE (5-20 nmol/mg protein/hour) than PlsC and an optimal pH range from 7.4 to 7.9.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphological adaptive changes of small intestinal tract regions due to pregnancy and lactation in rats.

In order to know the adaptive changes of small intestine regions (duodenum, and proximal, medial and distal jejunum-ileum) due to the reproductive stage (virgin, pregnancy and lactation), the weight, mucosal proportion, mucosal DNA and protein contents and protein/DNA ratio in female Wistar rats were measured. Pregnancy induces hypertrophy of the proximal half of the small intestine (duodenum and proximal jejunum-ileum), whereas lactation induces hyperplasia in all small intestinal regions and also hypertrophy but only in the duodenum.

Neural mediation of cholera toxin-induced mucin secretion in the rat small intestine

We examined the role of enteric nerves in cholera toxin (CT)-induced mucin secretion in proximal and distal regions of rat small intestine. Stimulation of intestinal loops with 120 micrograms (1.5 mumol) CT using an in vitro open-loop model resulted in an approximately four-fold increase in luminal mucin content over unstimulated controls in both regions of the gut. Prior treatment of loops with tetrodotoxin had no effect on the amount of mucin released in response to CT. However, permanent destruction of primary sensory afferent nerves by neonatal treatment of rats with capsaicin reduced the mucin response to CT to baseline levels in both regions. In normal animals, atropine resulted in approximately 40% inhibition of mucin secretion in both the proximal and distal small intestine. The atropine-sensitive secretory response appears to be a component of the capsaicin-sensitive response. These results suggest that choleraic mucin secretion is mediated primarily by a capsaicin-sensitive neurogenic pathway involving local activation of sensory nerves, which may then elicit mucin secretion through interaction with cholinergic nerves.