Mechanism Of Intestinal Absorption Research Articles

Absorption of Keto-Analogues of Branched-Chain Amino Acids from Rat Small Intestine

The keto-analogues of essential amino acids provide a source of essential amino acids that contain no nitrogen, but little is known about the mechanism of keto-analogue intestinal absorption. Absorption of the keto-analogue of valine was compared with that of the corresponding amino acid valine by perfusing rat jejunum and ileum in vivo. In both ileum and jejunum, keto-valine was absorbed at rates only moderately below those of the amino acid valine when perfused at 1–50 mM. In the jejunum, absorption rates for keto-valine relative to valine ranged from 73% to 39% at perfusate concentrations of 1 mM and 25 mM, respectively. Similar results were obtained in the ileum. The absorption curve of keto-valine was nonlinear at low perfusate concentrations and linear at higher concentrations, consistent with both saturable transport and passive diffusion. In further studies, 3 mM keto-valine was perfused into jejunal segments. Twenty-five millimolar of the keto-analogues of isoleucine and phenylalanine inhibited keto-valine absorption by 43% and 50%, respectively, whereas 3 mM of the keto analogue of isoleucine did not. Sixty-seven millimolar valine and 56 mM glucose significantly increased keto-valine absorption by 30% and 57% respectively; there were corresponding fourfold and eightfold increments in water transport. The keto analogues of leucine and isoleucine were absorbed at the same rates as keto-valine when perfused at 3 mM and 25 mM. Arterial and mesentric venous blood was sampled after perfusing 25 mM of keto-leucine and keto-isoleucine. There was a significant release of the corresponding amino acids into mesentric venous blood compared with controls, which suggest partial transamination during absorption. The data indicate: (a) Keto-analogues of the branched-chain amino acids are absorbed at rates moderately below those of the corresponding amino acids; (b) keto-valine absorption is in part mediated throught a saturable mechanism; (c) keto-valine absorption is influenced by solvent drag; and (d) partial transamination occurs during keto-analogue absorption in the rat jejunum.

Intestinal absorption of several beta-lactam antibiotics. II. Absorption characteristics of amino-penicillins and amino-cephalosporins.

In order to investigate the absorption characteristics of cephalexin, cephradine, and amoxicillin, which are well absorbed from the gastrointestinal tract, the mechanisms of intestinal absorption of these antibiotics in rats were examined using the recirculating perfusion technique, the loop method, and the everted gut sac technique. Cephradine was shown to be actively transported. Other antibiotics appeared to diffuse across the intestine down a concentration gradient. The accumulations of these drugs, in the intestinal tissue, especially cephalexin and cephradine, were particularly marked, and the accumulation of each of these three drugs was significantly inhibited at low temperature. These observations provide an experimental basis for the known rapid absorption of these antibiotics.

Arachidonic acid intestinal absorption: mechanism of transport and influence of luminal factors of absorption in vitro.

The mechanism and characteristics of intestinal absorption of arachidonic acid were studied in vitro using everted intestinal sacs of the rat. Arachidonic acid absorption was studied at concentrations of 5 micron to 8.36 mM. The plot of absorption rate vs. concentration fitted best to a rectangular hyperbola at low micron concentrations and to a straight linear relationship in the mM range of concentrations. Metabolic inhibitors and uncouplers did not change absorption in either range of concentrations. The absorption of arachidonic acid increased with thinning of the unstirred water-layer, decrease in the pH, or the substitution of sodium taurocholate by Pluronic F 68 OR Tween 80. Absorption decreased following the equimolar additions of oleic, linoleic, and linolenic acids. Absorption rate did not change when the taurocholate concentration was varied from 5-15 mM or following the additions of butyric or glutamic acids, leucine, lysine, or dextrose. It was concluded that arachidonic acid is absorbed by a concentration-dependent dual mechanism of transport which is not energy dependent. At the low micron range of concentrations, facilitated diffusion is predominant, while at mM concentrations, simple diffusion is the dominant mechanism of absorption. Changes in the intestinal fluid composition, flow rate, and pH can modify the rate of absorption of arachidonic acid.

Effects of free fatty acids as membrane components on permeability of drugs across bilayer lipid membranes. A mechanism for intestinal absorption of acidic drugs

Studies of the influence of fatty acids, which were the component of intestinal mucosal lipids, on the permeability of several drugs across bilayer lipid membranes generated from egg phosphatidylcholine and intestinal lipid have been pursued. The permeability coefficients of p- aminobenzoic acid, salicylic acid and p- aminosalicylic acid (anionic-charged drug) increased when fatty acids such as lauric, stearic, oleic, linoleic and linolenic acid were incorporated into the bilayer lipid membranes generated from phosphatidylcholine. In the presence of methyl linoleate and oleyl alcohol, no enhancing effect on p- aminobenzoic acid transfer was obtained. The effect of fatty acids was more marked at pH 6.5 than at pH 4.5. In contrast, upon the addition of fatty acids to intestinal lipid membranes which originally contained fatty acids, the permeability coefficient of p- aminobenzoic acid tended to decrease, though the permeability through intestinal lipid membranes was larger than that of phosphatidylcholine membranes. The permeability of p- aminobenzoic acid across bilayer lipid membranes from intestinal phospholipids was significantly decreased to about equal that of phosphatidylcholine membranes, and reverted to the value of intestinal lipid membranes when fatty acids were added to intestinal phospholipids. It seemed reasonable to assume that free fatty acids in the intestinal neutral lipid fraction could contribute to the increase in the permeability of p- aminobenzoic acid. On the basis of above results, possible mechanisms for good absorbability of weakly acidic drugs from the intestine are discussed.

The absorption of the keto acid analogues of the branched chain amino acids from rat shall intestine

THE ABSORPTION OF THE KETO ACID ANALOGLIES OF THE BRANCHED CHAIN AMINO ACIDS FROM RAT SMALL INTESTINE, F. L. Weber, Jr., and S. Desk*, V.A. Hospital and the University of Kentucky School of Medicine, Lexington, Kentucky. The keto acid analogues (KAA's) of essential amino acids, given orally, are promising agents in the treatment of uremia, portal systemic encephslopathy, and urea cycle enzyme deficiencies. They provide a source of essential amino acids which contain no nitrogen. But, little is known about the mechanism of KAA intestinal absorption. The mechanism of absorption of the KM of valine (K-val) was compared to the corresponding amino acid valine (val) by perfusing rat jejunum and ileum in viva. Keto acids -were determined spectrophotometrically or by gas-liquid chromatography. In both ileum and jejunum K-val was absorbed at rates only moderately below those of the amino acid valwhen perfused at l-50 mM. In the jejunum, absorption rates for K-val relative to val ranged from 7339% at perfusate concentrations of 1 and 25 mM respective1Y. Similar results were obtained in the ileum. There was a plateauing in K-val absorption rates at higher perfusate concentrations suggesting saturable transport. In further studies, 3 ml+! K-vsl was perfused into jejunal segments. Twenty-five mM of the KAA's of isoleucine and phenylslanine (structural analogues of K-val), inhibited K-val absorption by 43 and 50% respectively while 3 mM of the KAA of isoleucine did not. Sixty-seven mu val and 56 mM glucose significantly increased K-val absorption by 30 and 57% respectively, while there were corresponding kfold and f&fold increments in water transport. The KAA's of leucine and isoleucine were absorbed at the ssme rates as K-val when perfused at 3 and 25 mM. Arterial and mesenteric venous blood was sampled after perfusing 25 mM of the branched chain KAA's. There was a significant release of the corresponding amino acids into mesenteric venous blood compared to controls suggesting partial transamination during absorption. The data indicate: (1) K-val absorption is in part mediated through a saturable mechanism, distinct from the val carrier. (2) K-val absorption is influenced by solvent drag. (3) Partial transsmination occurs during KAA absorption.

Mechanism of intestinal absorption and brain uptake of L-5-hydroxytryptophan in rats, as compared to those of L-3,4-dihydroxyphenylalanine.

L-5-Hydroxytryptophan (5-HTP) and L-3, 4-dihydroxyphenylalanine (DOPA) were comparatively investigated of their mechanisms of intestinal absorption, metabolism in the intestine and liver tissues and mechanisms of passage through the blood-brain barriers, by means of in vitro and/or in situ techniques using rat tissues. The corresponding D-isomers were also investigated for comparison. L-5-HTP, but not the D-isomer, was found to be absorbed from the intestine by an active transport mechanism in the same way as L-DOPA. In vitro studies using rat brain cortex slices proved that both L-5-HTP and L-DOPA, but not their D-isomers, are taken up by the brain tissues by an active transport mechanism which is saturable, energy-dependent and competitive. There was no substantial difference between L-5-HTP and L-DOPA in the rate of intestinal absorption and that of brain uptake. It was indicated, however, that L-5-HTP was decarboxylated in the intestine to a much less extent than L-DOPA during the absorption and the decarboxylation activity of rat intestine and liver homogenates was found to be about four and seven times higher for L-DOPA than for L-5-HTP, respectively. The latter results suggest that the oral dose of L-5-HTP can be much more easily transferred into the circulating blood without being suffered from decarboxylation in the peripheral organs than L-DOPA, resulting in a more efficient penetration of L-5-HTP into the brain as a serotonine precursor.

Intestinal absorption mechanisms of ampicillin derivatives in rats. I. Intestinal absorption of ampicillin derivatives.

In order to investigate the reasons why the body fluid concentrations of pivampicillin and amoxicillin were higher than those of ampicillin after administration of the drugs to rats and humans, the mechanisms of intestinal absorption of these antibiotics in rats were examined using the new fluorometric determination method. In these experiments, it was found that the higher lipid solubility and the greater dissolution rate of pivampicillin are the main reasons for the higher body fluid concentrations of ampicillin after administration of pivampicillin. However, the higher body fluid concentrations of amoxicillin could not be explained on the basis of these physicochemical properties. In the studies using the rat small intestinal segments, i.e. the everted intestine, everted sac and the intact intestinal loop, greater binding to the mucosa of amoxicillin than of ampicillin was observed. This observation may provide an explanation for the difference in body fluid concentrations of these two drugs. These two amphoteric penicillins may be absorbed from the rat small intestine by passive diffusion mechanism.

3120. Absorption of macromolecules in the newborn: Martinsson, K. & Jönsson, L. (1975). On the mechanism of intestinal absorption of macromolecules in piglets studied with dextran blue. Zentbl. Vet Med. A 22, 276.

3120. Absorption of macromolecules in the newborn: Martinsson, K. & Jönsson, L. (1975). On the mechanism of intestinal absorption of macromolecules in piglets studied with dextran blue. Zentbl. Vet Med. A 22, 276.

Intestinal Absorption of Phosphate: Action of Protein Synthesis Inhibitors and Glucocorticoids in the Rat

The effect of actinomycin D, cycloheximide and glucocorticoids on the intestinal absorption of phosphate was studied. The effective intestinal absorption of 32P and 47Ca was determined simultaneously in intact rats in vivo using a whole body counter. Both, actinomycin D and cycloheximide caused a significant diminution of the intestinal absorption of phosphate whereas calcium absorption was not altered. Experiments with the in situ ligated loop technique were performed to eliminate the possibility that the action of the protein synthesis inhibitors could be due to an altered intestinal motility effect. Phosphate absorption was also significantly diminished under this condition. On the other hand, the administration of glucocorticoids produced a significant inhibition of phosphate and calcium absorption in the rat in vivo. The reported results indicate that proteins and/or enzymes with a rapid turn-over are involved in the mechanism of phosphate intestinal absorption, and confirm previous observations that phosphate and calcium are transported across the intestine by different mechanisms.

Parathyroid Hormone and Calcitonin: No Direct Effect on Vitamin D3-Mediated, Intestinal Calcium Absorptive Mechanism

Embryonic chick duodenum maintained in organ culture responds to vitamin D3 in the culture medium by increased cyclic AMP concentration, de novo synthesis of a specific calcium-binding protein and by increased uptake and transmucosal transport of radiocalcium. The presence of bovine PTH, porcine or salmon calcitonin had no effect on these intestinal responses suggesting that these hormones may have no direct effect on the vitamin D3-mediated, intestinal calcium absorptive mechanism.

Intestinal absorption of polyunsaturated phosphatidylcholine in the rat.

The mechanism of intestinal absorption of polyunsaturated phosphatidylcholine in an oil medium was studied with 1,2-di-[9,10,12,13-3H4]linoleoyl-sn-glycero-3-phospho-[N-14CH3]-choline, 1-[1-14C]linoleoyl-2-[9,10,12,13-3H4]-linoleoyl- and 1-[9,10,12,13-3H4]linoleoyl-2-[1-14C]linoleoyl-sn-glycero-3-phosphocholine, especially with regard to the stability of the ester bonds in position 1 and 2 of the phospholipid molecule. The absorption rate, as measured by the disappearance from the gastro-intestinal tract, was comparatively rapid in the first 6 - 8 h, but then became considerably slower. After 24 h more than 90% of the applied radioactivity was absorbed from the intestinal tract. Respiratory 14CO2 from the degradation of the unsaturated acyl moiety in position 2 is produced much more rapidly than that from the acyl group attached to the 1-position of the glycerophosphocholine backbone. Analyses of the liver phosphatidylcholine by specific enzymatic hydrolysis with phospholipase A2, 6 h after the application, showed that in the isolated PC 9 times more labelled fatty acids from the original 1-position were present than from the corresponding 2-position. In rats with lymph fistula it was shown that more than 90% of the acyl moieties of the administered 1,2-di-[9,10,12,-13-3H4]linoleoyl-[N-14CH3] glycerophosphocholine was transported by the chylomicrons. About one half of the 14C choline radioactivity of the glycerophosphocholine backbone was found in the chylomicrons and the other half in the liver. The 3H radioactivity distribution in the chylomicrons amounted to 25% in the phosphatidylcholine fraction and 75% in the neutral lipids. Positional specific analyses of the phosphatidylcholine present in chylomicrons confirmed the fact that the 1-position remained practically intact while the 2-position underwent considerable exchange with unlabelled fatty acids. Analysis of the liver of the animals with lymph fistula indicated that it was practically free of the 3H radioactivity derived from the acyl moieties but contained a high percentage of the 14C radioactivity of the choline group. The methyl groups of choline were oxidized only to a very small extent. These results demonstrate that during the absorption process, about one half of the absorbed polyunsaturated phosphatidylcholine is hydrolyzed to 1-acyl-lysophosphatidylcholine and reacylated again to phosphatidylcholine upon entering the mucosa cell, while the other half is completely hydrolyzed to free fatty acids and glycerophosphocholine or its hydrolysis products. The fatty acids released are utilized for the reassembly of triacylglycerides and phosphatidylcholine found in the chylomicrons.

Mechanism and Site of Small Intestinal Absorption of α-Tocopherol in the Rat

The site and mechanism of alpha-[5-methyl-3-H]tocopherol absorption was investigated using everted rat small bowel sacs incubated in a micellar medium. Mean plus or minus SE absorption rates of the vitamin at 300 muM incubation solution concentration by proximal, medial, and distal small bowel segments were 2.2 plus or minus 0.17, 3.4 plus or minus 0.21, and 2.0 plus or minus 0.04 nmoles per min per 100 mg, respectively. Addition of 2,4-dinitrophenol, sodium azide, or potassium cyanide to the incubation medium in separate experiments did not change the rate of absorption (P greater than 0.10). Stepwise increase in incubation solution tocopherol concentration up to 1200 muM resulted in a linear increase in the absorption rate. In all of the above described experiments the rate of absorption of the vitamin by the medial portion of the small bowel was significantly (P smaller than 0.01) higher than the rate of absorption of the vitamin by the proximal and distal small bowel segments. No transmural transport of the vitamin into the serosal compartment took place. Autoradiographic examination of the tissue after incubation disclosed accumulation of the vitamin in the submucosal lymphatic spaces. Alpha-Tocopherol absorption by the rat small bowel appears to be a passive diffusion process taking place at the highest rate in the medial portion of the small bowel.

Some Aspects of Vitamin D Action; Calcium Absorption and the Vitamin D-Dependent Calcium-Binding Protein

Publisher Summary This chapter examines calcium absorption and the vitamin D-dependent calcium-binding protein (CaBP). The investigations on the physiology of calcium absorption on CaBP indicated that there is nearly a 1:1 correspondence between the concentration of intestinal CaBP and the capacity of the intestine to absorb calcium. These correlations strongly indicate that CaBP has a significant role in the calcium translocation process. Calcium-binding protein of calf kidney was found exclusively in the cortex. Quantitative measurements on a single animal indicated that the concentration in the kidney cortex was about one-sixth that of the duodenum when expressed on the basis of total protein. Studies have shown that diphenylhydantoin and phenobarbital, the drugs used for anticonvulsant therapy of epileptics, are associated with the production of bone lesions in such patients if inadequate levels of vitamin D are provided. A unique system for the study of the intestinal calcium absorptive mechanism has been developed utilizing the embryonic chick duodenum maintained in organ culture.

Effect of some cationic drugs on the intestinal absorption of pralidoxime iodide.

The purpose of this study was to clarify the competition and the mechanism of intestinal absorption of various cationic drugs by in situ and in vitro techniques. As model drugs, pralidoxime iodide (2-PAM) and several amine drugs were employed. Although the absorption of 2-PAM and 2-allyloxy-4-chloro-N-(2-diethylaminoethyl) benzamide hydrochloride (A. C. D. B.) became saturated when drug concentration increased, they might not be absorbed actively. Nine amine drugs including A. C. D. B. competitively inhibited the absorption of 2-PAM. Furthermore, the absorption of A. C. D. B. was similarly inhibited by one of the amine drugs. No physicochemical interaction as well as direct action on the membrane permeability were observed. Since A. C. D. B. did not affect the absorption of quinine and L-tryptophan, its effect is thought to be brought on the specified drugs. Inhibitory action of the amine drugs on the accumulation of 2-PAM to the gut wall and the uptake to the epithelial cells were operative. Since pharmacologic action of amine drugs is so varied and the drugs with opposite pharmacologic action inhibit 2-PAM absorption as well, it is supposed that the molecular structures which amine drugs have in common (phenylalkylamine) may relate to the inhibitory effect. Other cationic drugs having no such group did not affect the absorption of 2-PAM at all.

The mechanism of intestinal absorption of phosphatidylcholine in rats.

1. The mechanism of absorption of phosphatidylcholine was studied in rats by injecting into the intestine phosphatidylcholine specifically labelled either in the fatty acid or in the glycerol moiety or with (32)P, when considerable amounts of 1-acyl-lysophosphatidylcholine were found in the intestinal lumen. 2-([(14)C]Acyl)phosphatidylcholine gave markedly more radioactive unesterified fatty acids in the lumen, compared with the 1-([(14)C]acyl) derivative. Some of the radioactivity from either the fatty acid or the glycerol moiety of the injected phosphatidylcholine appeared in the mucosal triacylglycerols. 2. Injection of (32)P-labelled phosphatidylcholine or (32)P-labelled lysophosphatidylcholine led to the appearance of radioactive glycerylphosphorylcholine, glycerophosphate and P(i) in the mucosa. 3. Rat mucosa was found to contain a highly active glycerylphosphorylcholine diesterase. 4. It was concluded that the dietary phosphatidylcholine is hydrolysed in the intestinal lumen by the pancreatic phospholipase A to 1-acylglycerylphosphorylcholine, which on entering the mucosal cell is partly reacylated to phosphatidylcholine, and the rest is further hydrolysed to glycerylphosphorylcholine, glycerophosphate, glycerol and P(i). The fatty acids and glycerophosphate are then reassembled to give triacylglycerols via the Kennedy (1961) pathway.

Hereditary disorders of intestinal transport.

Hereditary abnormalities of intestinal transport are rare conditions but are of disproportionate importance because of the information they give regarding the mechanisms of intestinal absorption in man. The main disability is usually diarrhoea, but there may be abnormalities from lack of absorption of an essential nutrient or occasionally from absorption of compounds in excess due to failure of a normal control mechanism. These diseases are experiments of nature which cannot be exactly simulated in the laboratory animal, and thus may on occasions give information unobtainable from other sources. More often, however, they confirm that the mechanisms of absorption studied in detail in smaller mammals are probably applicable to man. In some of these diseases there is an associated defect of transport in the proximal renal tubules as well as in the gut. They furnish evidence, therefore, that transport processes are closely related in the gut and in the kidney, or at least that an important step in transport is identical at the two sites.

Lipid absorption and deposition in rainbow trout (Salmo gairdnerii).

Rainbow trout, fed or starved for 5 weeks, were force-fed 23 μCi 1-14C-palmitic acid and sacrificed at [Formula: see text], 1, 2, 4, 8, and 14 h after feeding. Analysis of the blood suggested that trout possess an intestinal absorption mechanism for lipid that is very different from that found in other animals. The fish, incapable of delivering triglyceride to its circulation in the usual way, receives most of its absorbed lipid as free fatty acids, probably via the portal system. It was also found that light muscle more easily yielded its triglyceride stores, in agreement with its role as the major lipid depot in trout. Nonetheless, dark muscle was metabolically more active in deposition of muscle lipids. Dark muscle appeared to function more as an organ than a kinetically responsible contractile body.

Mechanism of intestinal absorption of drugs from oil in water emulsions. II. Absorption from oily solutions.

Drug absorption from oily solutions was investigated by the rat large intestine using in situ re circulation technique. Three model drugs (acetanilide, sulfapyridine, and salicylamide) and three different kinds of oil (isopropyl palmitate, ethyl laurate, and diethyl phthalate) were chosen for absorption studies.It was found that in oily solution, drug absorption through the large intestinal membrane usually took place after being liberated from oil into the secreting fluid.In the absorption of a drug having oil/water partition coefficient of less than one, apparent enhancement in the absorption was observed. This was attributed to the small volume of secreting fluid (aqueous phase) and the local concentration build-up of a drug at the absorptive surface.Some comparisons have been made with the absorptive behavior of drugs from oil in water emulsions.

Mechanism of intestinal absorption of drugs from oil in water emulsions. I.

Mechanism of the absorption of drugs from oil in water emulsions was studied in the rat large intestine. Synthesized esters of fatty acids and phthalic acid-0.1% Polysorbate 80 was chosen as the emulsion system, the oil/water volume ratio was varied from 0 to 1, and the absorption from emulsions of sulfapyridine, salicylamide, and of acetanilide was investigated using in situ recirculation and loop techniques.In the absorption of drugs having partition coefficients of larger than one, amount of drugs in aqueous phase rather than their concentrations was a critical factor for the absorption from oil in water emulsions.In the absorption of poorly oil-soluble drugs, drug absorption from emulsions was larger than the one from aqueous solutions when the overall volume of emulsions was kept constant, which suggested the importance of absolute volume of aqueous phase in the absorption of drugs from such systems.Usually drugs dissolved in oil were absorbed mainly via aqueous phase.

Calcium absorption and the vitamin D3-dependent calcium-binding protein

Normal 2-week-old chicks, when fed a low-calcium (0.1%), vitamin D3-replete diet containig stable strontium at a level equimolar to 1.2% calcium, developed a severe rachiticlike condition within 7 days. Whereas formerly it was suspected that “strontium rickets” resulted from direct inhibition of calcification only, it was shown that, preceding any detectable bone change, strontium inhibited vitamin D3-induced CaBP production and, simultaneously, the intestinal calcium absorptive mechanism. The results suggest the possibility that this effect of strontium may be due to its interference with the normal mechanism of calcium regulation of CaBP synthesis.