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Effect of vasoactive intestinal peptide, somatostatin, neurotensin, cholecystokinin octapeptide, and secretin on intestinal absorption of amino acid in rat.

The effects of vasoactive intestinal peptide (VIP), somatostatin (SRIF), neurotensin (NT), cholecystokinin octapeptide (CCK-8), and secretin (SEC) on the intestinal absorption of amino acid were investigated. Six groups of Wistar rats were studied: (1) controls; (2) VIP treated; (3) SRIF treated; (4) NT treated; (5) CCK-8 treated; (6) SEC treated. [3H]Leucine was given intraluminally through a cannula at the ligament of Treitz, a number of blood samples were obtained through a superior mesenteric vein catheter 1-60 min after administration of [3H]leucine, and the radioactivity of plasma was measured to evaluate the absorption of [3H]leucine. It was shown that VIP and SRIF significantly inhibited the absorption of [3H]leucine (by 59.1% and 38.7%, respectively), whereas NT, CCK-8, and SEC significantly enhanced absorption (by 44.2%, 49.6%, and 39.1%, respectively). Radioimmunoassays of VIP, SRIF, and NT showed that at least some of the hormones or peptides exerted their effects on absorption of leucine at or near their physiological concentrations.

Animals↗

Tea catechins decrease micellar solubility and intestinal absorption of cholesterol in rats.

A(-)-epicatechin (EC) and (-)-epigallocatechin (EGC) mixture and a mixture of their gallates (ECG and EGCG, respectively) markedly lowered lymphatic cholesterol absorption in rats with a cannulated thoracic duct. A mixture of ECG and EGCG was more effective in reducing cholesterol absorption than the EC and EGC mixture. These catechins also tended to decrease lymphatic absorption of triacylglycerols, although not so pronounced as in cholesterol absorption. An in vitro study on micellar solubility of cholesterol showed that these catechin mixtures precipitated cholesterol solubilized in mixed bile salt micelles in a dose-dependent manner. A mixture of ECG and EGCG more effectively precipitated micellar cholesterol than a mixture of EC and EGC. When purified EC, EGC, ECG and EGCG were used, EGCG was more effective in precipitating micellar cholesterol than ECG. The effect of EC and EGC was comparable and weaker than their gallate esters. The bile acid concentration in the micelles was not affected by these catechins. A positive correlation was observed between the amount of coprecipitated EGCG and cholesterol. These results clearly show that tea catechins, in particular their gallate esters, effectively reduce cholesterol absorption from the intestine by reducing solubility of cholesterol in mixed micelles. The observation accounts for the hypocholesterolemic effect of tea catechins.

Animals↗

Intestinal absorption of alpha-methyldopa: in vitro mechanistic studies in rat small intestinal segments.

The mechanism of intestinal uptake of alpha-methyldopa (Aldomet) was investigated using isolated segments of rat small intestine. Incubations were limited to 2 to 5 min as histological examination of the tissue showed significant loss of structural integrity after 10 to 20 min at 37 degrees C. alpha-Methyldopa in the tissue was extracted and assayed by high-pressure liquid chromatography. Corrections were applied for uptake into extracellular spaces using inulin (14C). Uptake was temperature- and concentration-dependent (Km congruent to 10 mM), was dependent on the location in the small intestine and was inhibited by ouabain (2 mM) or lack of sodium or glucose in the incubation medium. alpha-Methyldopa uptake also was inhibited by other neutral amino acids. The mucosal cell layer accounted for approximately 50% of the total drug accumulated in the tissue. Uptake was less when the serosal surface was exposed than when the tissue was everted. The similarity in uptake parameters between alpha-methyldopa and L-phenylalanine (parallel experiments) suggests that alpha-methyldopa is principally absorbed into rat small intestinal mucosal cells via an amino acid transport system.

Amino Acids↗

Ultrastructural changes in the lysosomes of rachitic intestinal absorptive cells.

In chicks maintained on a rachitogenic (vitamin D deficient) diet, the number of intestinal absorptive cell calcium-lysosomes is markedly decreased in comparison to normal animals. In addition, the majority (better than 50%) of these rachitic calcium-lysosomes are atypical in their fine structure resembling the lamellar bodies seen in certain diseases (Tay-Sachs disease, Duchenne's muscular dystrophy). Such atypical organelles are characterized by their internal membranous swirls reminiscent of myelin figures. This information appears to be a further indication that lysosomes are normally involved in calcium homeostatic mechanisms and therefore sensitive to circulating vitamin D levels.

Animals↗

Assessment and modulation of acamprosate intestinal absorption: comparative studies using in situ, in vitro (CACO-2 cell monolayers) and in vivo models.

The purpose of this study was to explore the intestinal absorption mechanism of acamprosate and to attempt to improve the bioavailability (BA) of the drug through modulation of its intestinal absorption using two enhancers (polysorbate 80 and sodium caprate) based on in situ, in vitro and in vivo models and comparing the results obtained. Intestinal transport of the drug, in the absence and in presence of polysorbate 80 (0.06, 0.28 and 9.6 mM) or sodium caprate (13 and 16 mM) was measured by using an in situ rat gut technique and Caco-2 cell monolayers. Additionally, the effect of sodium caprate on drug oral bioavailability, measured as urinary recovery, was quantified by performing in vivo experiments with the rat as animal model. Only sodium caprate was able to increase the absorption rate constant (ka) of acamprosate in the mid-intestine of the rats from 0.29 +/- 0.07 h-1 in the absence of the promoter to 0.51 +/- 0.19 h-1 in the presence of C10 16 mM, along with the apparent permeability (Papp) obtained in Caco-2 cells (around two-fold). However, the drug bioavailability in rats (around 20%) did not improve in the presence of any of the concentrations tested (13, 16 and 50 mM). It is concluded that acamprosate absorption likely occurs via paracellular pathway and can be enhanced by sodium caprate in situ and in vitro but not in vivo-thus suggesting that although in situ and in vitro studies could be useful in early screening to select a potential promoter, in vivo studies in animal models are necessary to confirm the utility of the enhancer and to determine the influence of physiological variables.

Acamprosate↗

Intestinal absorption of dolichol from emulsions and liposomes in rats.

The intestinal absorption of dolichol from various dosage forms was investigated using the intestinal loop and everted sac methods in the rat. The in situ loop experiments showed that the absorption of dolichol from a triglyceride emulsion was dependent on the chain-length of the triglyceride; the absorption from a tri-n-butyrin emulsion in 1 h was 18.0% of the dose; and the absorption from an HCO-60 suspension was 4.3%. The liposomal preparation enhanced the absorption up to 39.1% of the dose. In in vitro experiments, 25.0% and 13.2% of dolichol were taken up by everted sacs of the jejunum and the ileum, respectively. On the other hand, phospholipids composing liposomes were not absorbed under these conditions. The above results suggest that the absorption mechanism from liposomal preparations may be as follows: dolichol is released from the liposomes into the aqueous phase adjacent to the surface of the intestine and is subsequently partitioned into the intestinal tissue.

Animals↗

Effect of chlorpromazine on intestinal absorption of sulfamethoxazole in rats.

The effect of chlorpromazine (CPZ) on the intestinal absorption of sulfamethoxazole (SMZ) was studied in isolated perfused rat small intestine by comparing two determinants, i.e. the epithelial permeability and the intestinal blood flow. The appearance rate of SMZ in blood in the presence of CPZ decreased to one-half of the control without CPZ. The pH of perfusion solution was significantly decreased by CPZ after 10 min perfusion. According to the Winne's absorption model, CPZ did not change the apparent epithelial permeability of SMZ, but decreased the epithelial permeability of unionized SMZ due to the decrease in the pH of perfusion solution by CPZ. It was also suggested that CPZ decreased the fraction of the total blood flow rate in the subepithelial capillaries to less than one-half.

Animals↗

Effect of food intake on intestinal absorption and mucosal hydrolases in alloxan diabetic rats.

The relation between food intake and enzyme activity of the small intestine and rate of intestinal absorption were studied in rats 15 days after induction of alloxan diabetes. Diabetic rats were given an ad lib. semisynthetic diet or a restricted diet on the basis of either daily intake or body weight. The rates of absorption of 5 mMD-galactose and L-valine were determined in vitro by the everted sac method. The rates of absorption of the substances, expressed per unit weight or per length of intestine, were higher in diabetic rats than in controls, regardless of the amount of food consumed. Maltase and sucrase activities were significantly increased in diabetic rats, regardless of the amount of food consumed. The activity of intestinal alkaline phosphatase was increased in diabetic rats fed ad lib., but not in those on a restricted diet. These findings suggest that in alloxan diabetic rats the increased disaccharidase activity in the small intestine is due to insulin deficiency, and that the increased activity of alkaline phosphatase is only a secondary effect of insulin deficiency, caused by increased food intake resulting from insulin deficiency.

Alkaline Phosphatase↗

Increased intestinal absorption of oleic acid with aging in the rat.

Changes in nutrient absorption could be responsible for some of the disorders associated with aging. Oleic acid is the most common dietary fatty acid. Therefore, we investigated its absorption by the small intestine of aging rats in vivo. We used a single pass intestinal perfusion technique to study absorption in animals between 6 and 138 weeks of age. Rats less than 70 weeks of age absorbed 14,000 to 15,000 nmol of oleic acid per 100 cm/hr. In contrast, rats 94 weeks of age or older, absorbed 22,000 to 23,000 nmol of oleic acid per 100cm/hr. The 61% increase in oleic acid absorption as the rats aged correlated with a decrease in the resistance of the unstirred water layer from 0.8 to 0.5 min/cm3/100cm. Concomitantly, the surface area of the unstirred water layer increased from 97.1 to 141.2 cm2/100cm. The changes in unstirred water layer resistance and surface area explain the observed increase in absorption of oleic acid with aging. The increased surface area and decreased resistance of the unstirred water layer are both conducive to increased intestinal absorption of this lipid nutrient as the animals aged.

Aging↗