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PubMed1986

Intestinal absorption of tetramethylammonium and its derivatives in rats.

The intestinal absorption of tetramethylammonium (TMA) and its derivatives from rat jejunum has been investigated with an in situ loop method and an in vitro everted sac method. At a low concentration, TMA was absorbed rapidly from the in situ intestinal lumen without being metabolized in the tissue and the rate of absorption was dependent upon the concentration used. The profile of TMA absorption included two processes, i.e. saturable and non-saturable. The absorption of TMA was inhibited competitively by analogs that have a N-trimethyl group in their structure. Among them, choline showed the strongest inhibition to TMA absorption. The inhibitory potency of these analogs was related to their chemical structure. Although TMA was not transported into the intracellular fluid of the everted intestine against a concentration gradient, the tissue accumulation of TMA was inhibited by 2,4-dinitrophenol (2,4-DNP), a metabolic inhibitor, and was highly dependent upon the incubation temperature. These findings demonstrate that TMA is absorbed through the rat small intestine by a carrier mediated transport system. An apparent Kt of 0.73 mM and a maximum V of 11.5 nmol/g tissue wet wt/min were determined by an in situ loop method. It was also suggested that the endogenous quaternary ammonium compound, choline, might be absorbed by the same carrier system.

2,4-Dinitrophenol↗
PubMed1982

The Golgi apparatus of rat small intestinal absorptive cells. I. Morphology and cytochemical staining pattern in proximal and distal small intestinal regions.

Comparative studies on the Golgi apparatus of rat small intestinal absorptive cells from duodenal, jejunal and ileal segments showed that the characteristic polarity of Golgi stacks is apparent along the entire small intestine; dilated cisternae containing lipoprotein particles are preferably localized at one Golgi side (cis face); narrow, regular cisternae predominate at the other side (trans face). Osmium deposits after prolonged osmification are restricted to cis Golgi cisternae. Pronounced differences between proximal and distal small intestinal regions exist in the cytochemical staining pattern of Golgi stacks after localization of thiamine pyrophosphatase, inosine diphosphatase and acid phosphatase. In duodenal and proximal jejunal absorptive cells demonstration of thiamine pyrophosphatase and inosine diphosphatase causes heavy deposits of reaction product over all Golgi cisternae; in the distal jejunum and in the ileum only 1-3 cisternae at the trans Golgi side are reactive. Similarly, the number of acid phosphatase-positive cisternae decreases from proximal to more distal small intestinal regions. Thiamine pyrophosphate, nucleoside diphosphatase and acid phosphatase are assumed to be active in glycosylation being involved in the removal of uridine diphosphate and other nucleoside phosphates (Tartakoff, 1980; Farquhar and Palade, 1981; Roth and Berger, 1982). Accordingly, the differences in the Golgi apparatus staining pattern after localization of these enzymes between proximal and distal small intestinal segments may reflect regional differences in the glycosylation of apoproteins in lipoprotein particles and in the kinetics of glycosylated plasma membrane and lysosomal constituents.

Acid Anhydride Hydrolases↗
PubMed1999

Drug liposome partitioning as a tool for the prediction of human passive intestinal absorption.

PURPOSE: Appropriate physicochemical parameters are desired for the prediction of passive intestinal drug absorption during lead compound selection and drug development. METHODS: Liposome distribution coefficients measured titrimetrically and solubility data at pH 6.8 were used to characterize 21 structurally diverse ionizable drugs covering a range from <5% to almost complete absorption. RESULTS: A sigmoidal relationship was found between the percentage of human passive intestinal absorption and a new absorption potential parameter calculated from liposome distribution data and the solubility-dose ratio. In contrast, the human absorption data did not correlate with an octanol-based absorption potential or partitioning data alone. Poor correlations were found between liposome and octanol partitioning of ionic species or nonionic bases indicating the profound differences of the partitioning systems. CONCLUSIONS: Liposome distribution coefficients of ionizable drugs derived by a pH-metric titration were successfully used to calculate a parameter that correlates with the percentage of passive intestinal absorption in humans. Profound differences between liposome and octanol partitioning were found for a highly diverse set of species. This titration technique may serve to generate liposome partitioning data for the selection and optimization of lead compounds and in drug development.

Humans↗
PubMed1987

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↗
PubMed1992

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↗
PubMed1987

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↗
PubMed1981

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↗
PubMed1989

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↗
PubMed1983

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↗
PubMed1980

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↗
PubMed1983

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↗
PubMed1983

Impaired intestinal absorption of vitamin D3 in azotemic rats.

Changes in vitamin D metabolism and their effect on calcium and bone metabolism in uremia have been extensively studied. However, the possible effect of uremia on intestinal absorption of vitamin D has not been investigated. We determined the rate of intestinal absorption of vitamin D3 in uremic and normal rats using a well-defined in vivo perfusion technique under identical experimental conditions. The rate of jejunal absorption of vitamin D3 in uremic animals (5.09 +/- 1.87 pmol/100 cm/h) was significantly less (p less than 0.001) than that found in the control animals (11.5 +/- 1.6 pmol/100 cm/h). While the underlying mechanism(s) of the observed reduction in vitamin D absorption in uremia is not known, its recognition adds another dimension to the previously recognized abnormalities of vitamin D metabolism in uremia.

Animals↗
PubMed1993

Influence of anesthetic regimens on intestinal absorption in rats.

We compared the influence of anesthetic regimens using urethane (U), pentobarbital (P), ether (E), and ketamine/midazolam (K) on the intestinal absorption of several probes using a single-pass perfusion technique in rats. The selected probes were D-glucose (1 mM) for the resistance of the unstirred water layer (UWL), D-glucose (100 mM) for the capacity of carrier-mediated D-glucose transport, L-glucose, and urea for membrane-limited passive transport, and tritiated water (3H2O) for blood flow at the absorption site. The absorbed fraction of D-glucose (1 mM) was the smallest for U and the largest for P, suggesting that the resistance of UWL is the largest for U and the smallest for P. The absorbed fraction of D-glucose (100 mM) was the largest for P (U = E = K < P), suggesting a higher capacity of carrier-mediated D-glucose transport for P. The absorbed fraction of urea was similar for all anesthetics, while that of L-glucose was the smallest for K (U = P = E > K). Although the results for these two markers of membrane-limited passive transport were inconsistent, the passive permeability of the intestinal membrane may be lower when treating with K. The intestinal absorptions of D-glucose (1 and 100 mM), L-glucose, and urea were, in general, lower with any of the anesthetics than under nonanesthesia (N), suggesting increased resistance of UWL and decreased intestinal membrane permeability by carrier-mediated and passive transport under anesthesia. The only exception was the absorption of D-glucose (100 mM) under P, which was comparable to that under N.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗
PubMed1977

[Decrease of intestinal absorption of 47-calcium in chronic alcoholism].

Intestinal 47-calcium absorption has been studied in 34 chronic alcoholics, 17 of whom were cirrhotics (group A) and 17 non-cirrhotics (group B). These patients were compared with 44 normal subjects (group C). In group C, the 47Ca 2 h plasma % of the dose showed a significant negative correlation to the total body weight (p less than 0.001) and a positive correlation with the serum albumin (p less than 0.05). The mean intestinal absorption of 47Ca expressed as 2 h plasma % of the dose multiplied by total body weight was 131 +/- SD 52 in group A and 136 +/- SD 71 in group B. These two means are significantly low (p less than 0.001 and p less than 0.002 respectively) in relation to that found in group C (168 +/- SD 32). These results suggest that intestinal calcium absorption is diminished in chronic alcoholism even in the absence of hepatic cirrhosis.

Alcoholism↗
PubMed1995

Method to estimate the rate and extent of intestinal absorption in conscious rats using an absorption probe and portal blood sampling.

PURPOSE: A variety of methods exist which determine the rate and extent of intestinal absorption. The method described here employs an internal absorption reference probe and portal blood sampling in unanesthetized rat. METHODS: Theophylline and tritiated water were selected as absorption reference probes since they are quantitatively absorbed in conscious rat. The fraction of an intestinal dose which reaches portal blood was determined from the resulting portal-systemic blood concentration gradients of the drug relative to the absorption probe. The absorption probes provide a means to calculate the drug mass reaching portal blood without the need of measuring the portal blood flow rate. The technique was evaluated with verapamil and a well-absorbed 5-lipoxygenase inhibitor, A-79035. RESULTS: The fraction of an intrajejunal dose of A-79035 reaching the portal vein (FG) was 0.86 using theophylline as the absorption probe. Verapamil, which is susceptible to extensive hepatic first-pass elimination, was completely absorbed (FG = 0.98) within 1 hour, but was only 21.4% bioavailable. Absorption rate constants, estimated from initial appearance rates in portal blood, were used to monitor factors that affect drug absorption. For example, with a dose solution containing 30% PEG-400, the absorption rate constants of theophylline and A-79035 were significantly reduced. Anesthesia reduced the absorption rate constant for theophylline in rats by 40% compared to conscious animals. CONCLUSIONS: The technique detailed here allows reliable, direct measurement of intestinal absorption which may assist in characterizing oral dosing for novel therapeutic agents.

Animals↗