Sex variation in the activities of mucosal hydrolytic enzymes in the small intestine of the rat.

Mucosal response of alkaline phosphatase, ATPase and disaccharidase (lactase, maltase and trehalase) activities to sex hormones were studied by comparing male and female rats and castrated males and by injecting testosterone into castrated males. Alkaline phosphatase showed a very steep gradient in the small intestine from the oral to the aboral end, whereas ATPase activity in the ileum was still about 50% of that in the duodenum. Both enzymes showed only minor sex variations and weal response to castration. Lactase and maltase had peak activities in the jejunum, but trehalase activity was nearly equally high in the duodenal mucosa as in the jejunum. Jejunal lactase activity was about 50% lower in female than in male rats and castration decreased activity in males to the same low level as found in females. The administration of testosterone to castrated male rats did not enhance activity. Maltase activity showed similar sex variation, although castration was not able to decrease activity during the test period. Trehalase activity was lower in female than in male rats. The administration of testosterone enhance activity in castrated males.     

Inhibition of canine duodenal interdigestive myoelectric complex by nutrient perfusion of jejunal and ileal Thiry-Vella loops

The mechanisms by which the intestinal interdigestive myoelectric complex (IDMEC), recurring at about 90 minute intervals in the fasted dog, is disrupted by feeding remain unknown. We investigated whether the IDMEC could be disrupted in the duodenum by perfusing a Thiry-Vella loop with glucose in the dog. An intestinal Thiry-Vella loop, measuring one half (80 to 160 cm) of the total length of the small bowel was constructed in four dogs from the jejunum, and in four other dogs from the ileum. Extracellular nichrome electrodes were sewn on the duodenum for recording the electrical activity of the intestine. After three weeks' recovery, electrical recordings were performed in the fasted dogs in order to observe whether the IDMEC persisted in the duodenum when the Thiry-Vella loops were perfused, at different days, for four hours with solutions made of either (1) NaCl 154 mM, (2) NaCl 308 mM, (3) glucose 300 mM, or (4) glucose 600 mM, at a rate of 8 ml/min. NaCl 308 mM and glucose 600 mM were also delivered at a rate of 4 ml/min. Glucose output from the Thiry-Vella loops was measured throughout the experiments over consecutive five minute intervals. Each experiment was performed three times in each dog. The results showed that perfusing the Thiry-Vella loops with NaCl 154 mM or NaCl 308 mM did not suppress the IDMEC in the duodenum whether the flow rate was 4 or 8 ml/min. On the contrary, perfusing the jejunal loops with glucose 300 mM disrupted the IDMEC in 54% of the experiments; perfusing glucose 600 mM disrupted the IDMEC in 83% of the experiments. In the ileal Thiry-Vella loop experiments, the IDMEC was disrupted in 33% of the cases with glucose 300 mM and in 66% of the cases with 600 mM. No significant difference was observed with glucose 300 mM delivered at a rate of 8 ml/min and glucose 600 mM delivered at a rate of 4 ml/min. Finally, the inhibitory effect of perfusing the Thiry-Vella loops with glucose increased as the amount of absorbed glucose increased. These results indicate that interruption of the IDMEC by feeding probably involves extraintestinal factors. These factors do not seem to be specific for any one part of the small intestine, but they seem to be activated by intestinal absorption.     

Effect of pectin, a soluble dietary fiber, on functional and morphological parameters of the small intestine in rats

We investigated the effects of pectin, a soluble dietary fiber, on functional and morphological parameters of the small intestine in rats. A control group and a pectin-fed group were given a fiber-free elemental liquid diet and an elemental liquid diet containing 2.5% (w/w) pectin, respectively, for 2 weeks. The ileal mucosal specific activities of maltase, sucrase and alkaline phosphatase increased significantly in the pectin-fed group. Maltose absorption of the ileum, studied in vitro by the method of everted sacs and disaccharide-dependent potential difference, increased significantly in the pectin-fed group. The length of the small intestine as well as the villus height and crypt depth of both the jejunum and the ileum were significantly greater in the pectin-fed group. The crypt cell production rate of the jejunum and the ileum was also significantly greater in the pectin-fed group. Plasma enteroglucagon, but not gastrin, increased significantly in the pectin-fed group. These data suggest that pectin feeding results in hyperplasia of the small-intestinal mucosa and a significant increase in the enzyme activities of the brush border membrane of the ileum.     

Hepatotoxic Agent Thioacetamide Induces Biochemical and Histological Alterations in Rat Small Intestine

We have assessed the effect of the oral ingestion of thioacetamide on small intestine structure and function. Thioacetamide-treated rats showed diminished mucosa weight; protein, DNA, and RNA content; and leucine aminopeptidase activity as compared to controls in both jejunum and ileum. In the jejunum, there was a reduction in the activities of alkaline phosphatase, ATPase, glucose-6-phosphatase, and myeloperoxidase, whereas in the ileum, maltase, lactase, and -glutamyltranspeptidase were reduced. In both jejunum and ileum we found enlarged intercellular spaces, dark epithelial enterocytes, and lymphocyte infiltration. Enterocytes showed lobulated nuclei, deranged mitochondria with loss of their cristae, dilated rough endoplasmic reticulum containing dense material, and vesiculation of the smooth endoplasmic reticulum and the Golgi apparatus. Smooth muscle cells of the intestine exhibited ultrastructural alterations. These findings indicate that chronic oral intake of thioacetamide mimics not only hepatic alterations but also small intestine alterations normally associated with human cirrhosis.     

Activity distribution of seven digestive enzymes along small intestine in calves during development and weaning

Ten groups of calves were used to study the changes in activity levels and distribution of seven hydrolases in the intestinal mucosa during development and weaning. The calves in the first group were sacrificed at birth while those in the remaining nine groups were either milk-fed until slaughter on days 2, 7, 28, 56, 70, and 119; or weaned between days 28 and 56 and then slaughtered on days 56, 70, and 119, respectively. The small intestine was immediately cut off and divided into five segments, ie, duodenum, proximal jejunum, median jejunum, distal jejunum, and ileum. In the milk-fed animals, the activity levels of aminopeptidases A and N, alkaline phosphatase, lactase, and isomaltase were maximum at 2 days of age, and then declined sharply between days 2 and 7 but did not change significantly thereafter. By contrast, the maltase activity increased between days 7 and 119, while no sucrase activity was detected. Weaning resulted in a decrease in the activity of lactase and an increase in that of aminopeptidase N, maltase, and isomaltase. The distribution of all these enzymes along the small intestine was slightly influenced by age but not at all by weaning.     

Study of the effect of ileal distension on the motor activity of the jejunum, and of jejunal distension on the motor activity of the ileum

BACKGROUND/AIMS: The effect of ileal distension on the jejunal motor activity and ofjejunal distension on the ileal motility have been poorly addressed in the literature. We investigated the hypothesis that distension of either ileum or jejunum would affect the motile activity of the other. METHODOLOGY: Response of jejunal pressure to ileal balloon distension and of ileal pressure to jejunal distension in increments of 2 mL of normal saline were recorded in 18 dogs. The test was performed after individual local anesthetization of the ileum and jejunum and was repeated using saline instead of lidocaine. RESULTS: Ileal distension with 2, 4, and 6mL of saline produced no jejunal pressure response (p >0.05), while 8- and up to 12-mL distension effected jejunal pressure decrease (p<0.05). Jejunal distension up to 6mL did not change ileal pressure (p>0.05); distension with 8, 10, and 12 mL reduced it (p<0.05). Jejunal or ileal pressure responses were maintained as long as ileal or jejunal distension was continued. Distension of the anesthetized ileum or jejunum did not produce significant pressure changes in either. CONCLUSIONS: Jejunal or ileal pressure decrease and presumably hypotonia upon large-volume ileal or jejunal, respectively, distension postulate reflex relationship which we call 'ileal-jejunal and jejuno-ileal inhibitory reflex'. These reflexes appear to regulate chyme flow in small intestine by creating a balance of chyme delivery between the jejunum and ileum. Reflex derangement in neurogenic and myogenic diseases may result in gastrointestinal disorders, a point that needs to be investigated.     

Hyperplasia of Gastric Antral ß-Microseminoprotein Endocrine-like Cells and Increased Serum Levels of ß-Microseminoprotein in Atrophic Corpus Gastritis

The effect of fat emulsion in the upper intestine on the maximal gastric acid response to pentagastrin was studied in chronic gastric fistula (GF) mts with a 4-cm blind loop of the duodenum anastomosed to the jejunum (Roux-en-Y). Fat emulsion in the loop inhibited the acid response by 85%. To localize the site of the inhibitory mechanism, GF rats were provided with Thiry-Vella loops of the duodenum (bile and pancreatic ducts transplanted to the proximal jejunum) or with Thiry-Vella loops of the proximal jejunum and a Roux-en-Y loop of the duode* to prevent gastric juice from entering the duodenum. Perfusion of the duodenal loop with fat emulsion mixed with bile and pancreatic juice reduced the acid response by 49%, but perfusion of the proximal jejunal loop did not alter the response. It is concluded that the intestinal mechanism for inhibition of acid secretion by fat is located in the duodenum in rats.     

Duodenal acidification and jejunal hyperosmolality inhibit pentagastrin-stimulated acid secretion in chronic gastric fistula rats

In chronic gastric fistula (GF) rats, HCl and a hyperosmolal solution of polyethylene glycol (PEG) in the upper intestine inhibit pentagastrin-stimulated gastric acid secretion by different mechanisms, but their anatomic sites have not yet been established. In the present study GF rats were provided with Thiry-Vella loops of the duodenum and the bile and pancreatic ducts transplanted to the proximal jejunum, or with Thiry-Vella loops of the proximal jejunum. In the latter rats the duodenum was anastomosed as a blind loop to the jejunum to prevent any gastric juice from entering the duodenum. Duodenal loop perfusion with 0.20 M HCl inhibited the acid response to pentagastrin by 62%, but perfusion with 1200 mOsmol x kg-1 of PEG solution did not alter the response. In contrast, acidification of the proximal jejunal loop did not alter but hyperosmolality inhibited the response by 41%. The study shows that the mechanism for inhibition by intestinal acidification is confined to the duodenum and that for inhibition by hyperosmolality is located in the proximal jejunum--but whether only to the proximal part is unknown.     

IGF-1 stimulates mucosal growth in ileal Thiry-Vella fistulas

BACKGROUND/AIMS: We determined whether the trophic effects of IGF-1 (Insulin-like growth factor-1) on the small bowel mucosa are mediated by either nonluminal factors or endogenous luminal secretion. The gut hormone IGF-1 stimulates growth of small bowel mucosa. The mechanisms responsible for this trophic effect are not known. METHODOLOGY: Rats underwent construction of a Thiry-Vella fistula of ileum. On postoperative day 10, the two groups were subdivided to receive either saline (control) or IGF-1. After 7 days, rats were killed and the Thiry-Vella fistula was removed. The mucosa was scraped and weighed, and protein content and alkaline phosphatase activity was determined. RESULTS: IGF-1 significantly increased mucosal weight and alkaline phosphatase activity and protein content of ileal Thiry-Vella fistula compared with the control rats. CONCLUSIONS: IGF-1 mediated stimulation of small bowel mucosal growth is mediated by factors that are independent of luminal contents and pancreaticobiliary secretion. IGF-1 may prove to be an important enterotrophic factor for gut mucosal proliferation.     

Induction and maintenance of mucosal enterokinase activity in proximal small intestine by a genetically determined response to mediated sodium transport

Mucosal enterokinase activity was established at intervals throughout the small intestine in guinea-pigs; maximum activity was present in the duodenum and proximal jejunum in new born as well as adult animals. Transposition of 5 cm lengths of small gut from the high enterokinase containing proximal region to the distal intestine and vice versa showed that mucosal enterokinase activity in the transposed segments was little changed after several weeks of healthy life. Isolation of proximal jejunal loops from luminal continuity resulted in the fall of mucosal enterokinase activity to minimal levels within 16 hours. Low levels of mucosal enterokinase activity were identified in loops of both proximal and distal jejunum 12 weeks after isolation. Luminal perfusion studies in vivo in proximal jejunal loops 24 hours after isolation showed that mucosal enterokinase activity could be restored to near normal levels within four to six hours by luminal sodium in the presence of active pancreatic endopeptidases, oligopeptides, L-amino acids, or D-glucose but not D-amino acids or D-fructose. Near normal mucosal enterokinase activity persisted in the loops for as long as luminal perfusion with 144 mM sodium and L-lysine or trypsin was maintained (24 hours). The time course of the restoration of mucosal enterokinase activity was compatible with an initial precursor activation as well as biosynthesis. The requirement for luminal sodium appeared to be absolute regardless of the co-substrate and supports the conclusion that mucosal enterokinase activity is dependent on mediated sodium transport. The ability of proximal intestinal enterocytes to respond to sodium flux with an increase in enterokinase activity is a property determined in intrauterine life: distal intestinal enterocytes may have functioning structural genes for enterokinase but appear to be unable to respond.     

Prolactin and the small intestine. Effect of hyperprolactinaemia on mucosal structure in the rat.

To study the mechanism for the adaptive mucosal hyperplasia which occurs independent of luminal nutrition and pancreatico-biliary secretions in isolated Thiry-Vella segments of intestine from lactating rats, and to examine the effects of prolactin on small bowel mucosal structure in the rat, we used two models of experimental hyperprolactinaemia and compared quantitative histology and several markers of mucosal mass in jejunum and ileum from control rats and from test and lactating animals. Hyperprolactinaemia, induced by perphenazine injections (5 mg/kg/day for two or seven weeks) or transplantation of four pituitary glands from donor animals to beneath the renal capsule in the recipient, was confirmed by radioimmunoassay. Proof of its biological activity was obtained by weighing the mammary pads and by demonstrating true breast hyperplasia on histological section. Median serum prolactin levels increased from 50 ng/ml in the controls to 570 ng/ml in the perphenazine treated animals and to 600 ng/ml in the pituitary transplanted rats-levels comparable with those seen in lactation (870 ng/ml). In the lactating rats, there was striking mucosal hyperplasia of both jejunum and ileum but, despite the hyperprolactinaemia, there were no such changes in villus height, crypt depth, or in mucosal wet weight, protein, or DNA/unit length intestine in the perphenazine-injected or pituitary-transplanted animals. We conclude that prolactin is not atrophic to the intestine in rats and that hyperprolactinaemia cannot explain the intestinal adaptive changes of lactation.     

The influence of age on intestinal dipeptidyl peptidase IV (DPP IV/CD26), disaccharidases, and alkaline phosphatase enzyme activity in C57BL/6 mice

The objective of this study was to determine and describe the age-related changes in intestinal brush border membrane enzyme activities that occur in C57Bl/6 mice. Specifically, jejunal, duodenal, and ileal dipeptidyl peptidase IV/CD26, disaccharidase (lactase, sucrase, and maltase), and alkaline phosphatase activities were determined. A significant correlation between analyzed intestinal brush border membrane enzyme activities and animal age was found. Our study revealed that intestinal dipeptidyl peptidase IV/CD26, lactase, sucrase, maltase, and alkaline phosphatase activities decline significantly with age (p < .05). Nevertheless, the horizontal (duodenum to ileum) enzyme activity patterns are not affected by age.     

Differentiation status of rat enterocytes after intestinal adaptation to jejunoileal bypass.

The differentiation status of epithelial cells in intestinal adaptation remains unclear. To determine whether enterocytes reach optimum maturity following adaptation after 85% shortening of the rat gut by jejunoileal bypass surgery, activities of two brush border enzymatic markers of differentiation, alkaline phosphatase and sucrase, were examined in subpopulations of epithelial cells isolated sequentially from the villus/crypt axis of normal (sham operated) and hyperplastic mucosa. In jejunal villi, adaptational hyperplasia was associated with an increase in total epithelial alkaline phosphatase, but not total sucrase, activity; alkaline phosphatase activity increased most obviously in cells at the 11-50% position (from the tip) on villi. In hyperplastic ileal villi, total alkaline phosphatase activity fell, although sucrase activity did not change significantly. Specific activity (per mg protein) of sucrase on jejunal villus epithelium was reduced by the adaptational changes to bypass; alkaline phosphatase specific activity remained unchanged. In the ileum, despite adaptational changes to bypass, there was no increase in the normally low specific activities of sucrase and alkaline phosphatase. Bypass surgery did not change the major site of expression of either enzyme on jejunal or ileal villi. In conclusion, enzymatic markers of functional differentiation are not all equally affected by adaptational hyperplasia. Hypertrophy of villi and increased cell proliferation seen in jejunum remaining exposed to luminal contents resulted in an increase in the alkaline phosphatase but not the sucrase content. This is not, therefore, the result of a simple immaturity of villus cells. Morphological adaptation in the ileum, however, is not accompanied by adaptation of brush border enzyme markers of differentiation, confirming a functional immaturity of these cells. Strategies for increasing the expression of these markers may have clinical value.     

Calcium-binding activity of rat intestinal mucosa after massive small bowel resection.

Male Sprague-Dawley rats underwent resection of 50 cm of either proximal or distal small intestine or sham-operation. 6-7 weeks after operation mucosal calcium-binding activity was measured in segments of duodenum ileum and remaining 'midgut'. Similar measurements were obtained from weight and age-matched unoperated rats. There was no difference in calcium-binding activity between unoperated and sham-operated animals. After proximal resection the binding activity increased significantly in duodenum and midgut but did not change in ileum. After distal resection the binding activity decreased in duodenum but was unchanged in midgut and ileum. These studies show that mucosal calcium-binding activity undergoes changes but alteration of the binding activity in remaining gut varies with the location of the small bowel resection.     

The Influence of Age on Intestinal Dipeptidyl Peptidase IV (DPP IV/CD26), Disaccharidases,and Alkaline Phosphatase Enzyme Activity in C57BL/6 Mice

The objective of this study was to determine and describe the age-related changes in intestinal brush border membrane enzyme activities that occur in C57Bl/6 mice. Specifically, jejunal, duodenal, and ileal dipeptidyl peptidase IV/CD26, disaccharidase (lactase, sucrase, and maltase), and alkaline phosphatase activities were determined. A significant correlation between analyzed intestinal brush border membrane enzyme activities and animal age was found. Our study revealed that intestinal dipeptidyl peptidase IV/CD26, lactase, sucrase, maltase, and alkaline phosphatase activities decline significantly with age (p < .05). Nevertheless, the horizontal (duodenum to ileum) enzyme activity patterns are not affected by age.     

DISACCHARIDASE DEFICIENCY IN REGIONAL ENTERITIS

A man aged 32 years was found to have lactase deficiency in histologically normal jejunal and ileal mucosa, together with regional enteritis affecting the terminal ileum. The diseased ileum exhibited deficiencies of lactase, sucrase and maltase, and there was mucosal destruction. The remainder of the small intestine exhibited isolated lactase deficiency, a diffuse small intestinal defect the relationship of which to regional enteritis is uncertain.     

Rat intestinal iron transfer capacity and the longitudinal distribution of its adaptation to iron deficiency

The longitudinal gradient of intestinal iron transfer was investigated in normal and iron-deficient male Sprague-Dawley rats in vitro and in vivo. In normal rats in vitro iron transfer in the duodenum was approximately 3 times higher than in the jejunum and decreased in the ileum to approximately half the jejunal values. Compared to the controls in vitro iron transfer was increased 3-4 times in the duodenum and in the first jejunal segment and 2-3 times in the second jejunal segment. No significant adaptation to iron deficiency was found in the rest of the small intestine. Iron transfer rates showed the same longitudinal pattern when iron was chelated with nitrilotriacetic acid (NTA) or with ascorbate. The absorbed iron quantities, however, were approximately 5 times lower when Fe-ascorbate was used, which might be due to differences in bioavailability. Omission of Fe-NTA and Fe-ascorbate had no impact on the vitality of the segments. Glucose transfer was used as vitality criterion. It was not significantly different between corresponding iron-deficient and control segments. To control these results in vivo mesenteric blood was collected from duodenal and jejunal segments in situ. Corresponding to in vitro findings iron transfer was close to linear over the experimental period. In iron deficient duodenal segments iron transfer increased approximately 3 times as compared to controls while no adaptational changes were found in the distal jejunum. No significant longitudinal gradient was found in the mucosal content of ferritin and nonheme iron. Both parameters were decreased in iron deficiency by about half. The mucosal transferrin content showed no longitudinal gradient in control animals. In iron deficiency transferrin was significantly increased in the duodenum and in the three most proximal jejunal segments. The results indicate that in rats adaptation of iron absorption to the demand can only be expected in the duodenum and in the proximal 20 cm of the jejunum. Because this process shows a steep gradient in the proximal small intestine, studies on the adaptation of intestinal iron transfer to the demand should use short and well-defined segments in order to provide reproducible results.     

Regional localization of activity of Clostridium perfringens type A enterotoxin in the rabbit ileum, jejunum, and duodenum.

Rabbit ileal, jejunal, and duodenal loops were exposed to purified enterotoxin from Clostridium perfringens type A and then perfused for comparative analysis of effects of the enterotoxin on each region of the intestine. Ileal loops responded with enhanced net secretion of fluid and sodium, inhibition of chloride and glucose uptake, and substantial sloughing of epithelial cells. The jejunum responded with fluid secretion, enhancement of sodium secretion only during the first 20 min, inhibition of chloride and glucose uptake, and substantial sloughing of epithelial cells. In the duodenum, transport of fluid, sodium, and chloride was significantly altered only during the first 20 min of perfusion, and significant inhibition of glucose uptake varied from one period to another. Epithelial damage was much less than that seen in the jejunum or ileum. Levels of fluid protein in all three sections corresponded closely to extent of tissue damage. In general, it was found that the severity of response to fixed doses of enterotoxin varied as follows: ileum greater than jejunum greater than duodenum.     

Intestinal regrowth is amplified after jejunal but not ileal resection during tapeworm infection in the rat

The ileum possesses functions required by a healthy individual that are not fully supplanted by the duodenum or jejunum. Evidence suggests that the ileum may also be necessary to maintain an enteric parasite–host interaction. We hypothesized that the ileum is essential to the survival of the lumen-dwelling, rat tapeworm, H. diminuta. Male rats were divided into three groups: those with ileal or jejunal resections and nonresected controls. Half of each rat group was infected with the tapeworm. After jejunal resection, the weight but not length of intestinal remnant (duodenum + ileum) in infected rats returned to that of control, nonresected intestine 29 days after surgery and tapeworm numbers were fully maintained. In contrast, after ileal removal intestinal length and weight of the remaining duodenum and jejunum in infected rats were significantly decreased and tapeworm survival diminished. Data indicates that intestinal growth following resection is amplified by tapeworm infection when the ileum remains but diminished when the ileum is removed. Furthermore, loss of the ileum results in decreased infection intensity and dry weight of the tapeworm.     

Regional difference in intestinal adaptation after total colectomy as judged by the changes of mucosal Na−K ATPase,cyclic AMP,and transmural potential difference

Intestinal adaptation and its regional difference after total colectomy were investigated in dogs by measuring mucosal Na-K ATPase, cyclic AMP, and transmural electric potential difference (PD). Twenty-four weeks after the total proctocolectomy, Na-K ATPase activity and PD increased significantly in all intestinal sites, whereas cyclic AMP showed no significant changes. The regional difference in the remaining intestine was examined in the jejunum, ileum, and interposed jejunum (neorectum). Na-K ATPase activity showed no significant regional difference, but the largest increase was found to occur in the ileum. PD also increased markedly in the ileum and there was significant difference between the ileum and other intestinal sites. These facts suggest that the increased active ion transport mediated by mucosal Na-K ATPase and transmural PD in the ileum is closely related to the intestinal adaptation occurring after total colectomy and indicates a greater potential of the ileum for adaptive compensation than either jejunum or neorectum.