Sterol absorption by the small intestine

PURPOSE OF REVIEW: Cholesterol absorption is a selective process in that plant sterols and other non-cholesterol sterols are absorbed poorly or not at all. Recent research on the sterol efflux pumps adenosine triphosphate-binding cassette transporter G5 and adenosine triphosphate-binding cassette transporter G8 has not only provided an explanation for this selectivity, but also, together with the discovery of a new class of cholesterol absorption inhibitor, has yielded new insights into the mechanisms that potentially regulate the flux of cholesterol across the enterocyte. This review discusses these recent developments and their importance to the regulation of whole body cholesterol homeostasis. RECENT FINDINGS: Adenosine triphosphate-binding cassette transporters G5/8 regulate plant sterol absorption and also the secretion into bile of cholesterol and non-cholesterol sterols. Loss of adenosine triphosphate-binding cassette transporter G5/8 function results in sitosterolemia. Ezetimibe, a novel, potent and selective inhibitor of cholesterol absorption which is effective in milligram doses, lowers plasma plant sterol concentrations in sitosterolemic subjects, thus suggesting that this drug might be inhibiting the activity of a putative sterol permease in the brush border membrane of the enterocyte that actively facilitates the uptake of cholesterol as well as other non-cholesterol sterols. SUMMARY: Intestinal cholesterol absorption represents a major route for the entry of cholesterol into the body's miscible pools and therefore can potentially impact the plasma LDL-cholesterol concentration. The combined use of agents that inhibit the absorption and synthesis of cholesterol provides a powerful new approach to the prevention and treatment of atherosclerosis.     

Cytoskeletal control of calcium absorption across the rat small intestine

1. The effect of colchicine, cytochalasin-B and procaine on calcium transport across the rat small intestine was investigated. The results obtained show the following: 2. Colchicine and cytochalasin-B at different concentrations inhibited significantly (P less than 0.001) calcium accumulation in rat intestinal cells, whereas procaine at different concentrations increased significantly (P less than 0.001) calcium accumulation in the rat small intestine. 3. Unidirectional influx of calcium across the rat small intestine was significantly inhibited (P less than 0.01) in the presence of colchicine and cytochalasin-B in the preincubation medium. Procaine, on the other hand, caused a significant increase (P less than 0.01) in the unidirectional influx of calcium across the rat intestinal cells. 4. The cell water content was not altered in the presence of the different drugs indicating that the changes in calcium transport across the rat intestinal cells are not due to alterations in the structure of the cell membrane.     

Aluminium-induced impairment of transcellular calcium absorption in the small intestine: calcium uptake and glutathione influence

Aluminium (Al) has been recognised as a cause of bone tissue disorders. The aims of this work were to investigate: (i) whether Al affects calcium (Ca) entry into enterocyte, and (ii) the possibility that the Al effect upon calbindin-D-related Ca transport would be influenced by intestinal glutathione (GSH) levels. In isolated chicken duodenal enterocytes, 100 microM Al lactate produced a decrease in both, the maximum uptake rate and the affinity constant of 45Ca uptake (CaUPT). This effect of Al on CaUPT was concentration-dependent in the micromolar range, showing an inhibitory saturation type phenomenon which appeared to be higher at pH 6.5 than at pH 7.4, and was not modified by the Ca channel activators A23187 and capsaicin. The simultaneous administration of Al (50 mg elemental Al/kg body weight, as AlCl3) and GSH (10 mmol/kg body weight) to rats during 7 days, prevented the inhibitory effects of Al on Ca transport. The protective effect of GSH was accompanied by an increased duodenal calbindin-D9k expression. Experimental depletion of intestinal GSH by means of D,L-buthionin-[S,R] sulfoximine, a gamma-glutamylcystein-synthase inhibitor, given as a single i.p. dose of 2 mmol/kg body weight, enhanced the degree of reduction of Ca absorption ascribed to Al. Our results suggest that Al might interfere Ca uptake by enterocytes through a general effect on cell membrane, and that an oxidative stress state induced by Al would reduce intestine GSH level affecting calbindin-D function and/or synthesis, thus leading to a reduced transcellular Ca absorption in the small intestine.     

Enhanced glucose absorption in the rat small intestine following repeated doses of 5-fluorouracil

Many studies demonstrated that 5-fluorouracil (5-FU) treatment of rodents caused the damage of small intestine, resulting in the malabsorption, while we recently found that repeated administration of 5-FU to rats increased Na(+)-dependent glucose absorption in the small intestine. This study investigated the cause of enhanced glucose absorption. 3-O-methyl-d-glucose (3-OMG) absorption was examined using the everted intestine technique. d-Glucose uptake, phlorizin binding, Western blot analysis and membrane fluidity were examined using small intestinal brush-border membrane vesicles (BBMV). Repeated oral administration of 5-FU to rats increased Na(+)-dependent 3-OMG absorption in the small intestine, while alkaline phosphatase activity in the small intestine decreased. Na(+)/K(+)-ATPase activity of 5-FU-treated rats was about three-fold higher than that of control rats. Although the amount of Na(+)-dependent glucose co-transporter (SGLT1) in 5-FU-treated rats decreased, the overshoot magnitude of d-glucose uptake in BBMV was not altered. Maximum binding of phlorizin in 5-FU-treated rats was 1.5-fold larger than that of control rats, but not altered the maximal rate of d-glucose absorption, Michaelis constant of d-glucose and dissociation constant of phlorizin. The membrane fluidity of 5-FU-treated rats increased. The enhanced d-glucose absorption in 5-FU-treated rats seems to occur secondarily due to the activation of Na(+)/K(+)-ATPase activity in basolateral membranes (BLM). Because the amounts of SGLT1 in 5-FU-treated rats decreased, the increase of turnover rate of SGLT1 and/or an expression of unknown Na(+)-dependent glucose co-transporter with high affinity for d-glucose and phlorizin sensitivity would contribute to the enhancement of d-glucose transport in 5-FU-treated rats.     

Iron absorption by small intestine of chickens

Iron (Fe) absorption by three segments (duodenum, jejunum, and ileum) of the small intestine of chickens was studied by a perfusion technique in vivo in closed circuit using⁵⁹Fe Cl₃ and was related to the histological characteristics of each segment. The serosal transfers of Fe for the duodenum and jejunum were the same (14%/cm), but significantly different (p<0.05) from those of the ileum (9%/cm), which may be explained by the morphological and histological properties of the gut of chickens. However, the presence of Fe in blood and in liver was significantly lower after perfusion of the jejunum and ileum than after perfusion of the duodenum. It is concluded that chickens show an early adaptation of small intestine to Fe absorption in response to the considerable loss of Fe suffered during the laying process.     

Dietary magnesium increases calcium absorption of ovine small intestine in vivo and in vitro

The purpose of this study was to investigate whether or not an increase in dietary Mg intake increases Ca absorption in the ovine gastrointestinal tract. In an in vivo experiment, an increase in the infused MgCl2 level (0.0, 25.0 and 75.0 mg Mg x kg BW(-1) x day(-1) with 75.0 mg Ca x kg BW(-1) x day(-1) as CaCl2) into the rumen for ten days significantly decreased fecal excretion but increased urinary excretion (P < 0.05) of Ca in five castrated male sheep. Apparent Ca absorption tended to increase (P = 0.067) whilst the retention and plasma concentration of Ca were not changed. In an in vitro experiment with isolated segments from the rumen, upper jejunum, cecum and upper colon under the presence of an electrochemical gradient, the mucosal to serosal Ca flux rate was significantly greater in the presence of 60.0 mM as compared with 1.2 mM MgCl2 (P < 0.05). From these results, we conclude that the mucosal Mg has the ability to increase the Ca absorption in the gastrointestinal tract in sheep when the dietary Mg level is raised.     

Paracellular absorption of D-glucose by rat small intestine in vivo

D-glucose diffusion in both jejunum and ileum using a perfusion system in vivo was determined. 2,4,6-triaminopyrimidine (20 mM) induced an inhibition on D-glucose diffusion of 32% in the two segments of the small intestine studied. Glucose net efflux from the jejunum into the lumen was higher than that from the ileum. Phlorizin increased the sugar efflux in both areas.     

Enhancement by lactosucrose of the calcium absorption from the intestine in growing rats

The effects of dietary lactosucrose on calcium absorption from the intestine and calcium accumulation in bones were investigated in growing female rats. The apparent calcium-45 ((45)Ca) absorption, residual (45)Ca ratio in the body, and (45)Ca accumulation in the femur and tibia of lactosucrose-supplemented rats were significantly higher than in control rats 24 h after the administration of a (45)CaCl(2) solution.     

Effect of enzymatic treatment on calcium absorption by small intestine: a comparative study between rat and rabbit transport mechanisms

Calcium absorption by the small intestine of rat and rabbit reached steady state after 60 min of incubation with intracellular to extracellular ratio of 2.0. Trypsin and neuraminidase significantly inhibited (P less than 0.05) calcium accumulation in rat small intestine. These enzymes showed no significant effect (P greater than 0.05) on calcium transport across rabbit small intestine. The inhibitory action of trypsin and neuraminidase on calcium accumulation by the rat small intestine does not involve the influx of calcium into the intestinal cells.     

Electron probe analysis of calcium transport by small intestine

Calcium transport in small intestine of rat and chick has been studied at the cellular level using the electron probe X-ray microanalyzer. Tissues were examined directly after removal as well as after incubation in a calcium solution. In both preparations, discrete calcium localizations were found associated with intracellular and extracellular goblet cell mucus. The in vitro preparations showed calcium in transit across the absorptive epithelium in discrete localizations. Although the primary path of transport was along lateral cell borders, some localizations were found in the cytoplasm in a supranuclear position. The effect of vitamin D depletion and repletion was to decrease and increase, respectively, the number of calcium localizations in transit across the epithelium. These results suggest that calcium is transported while in a sequestered form and indicate that goblet cell mucus plays a role in this transport process.     

Difructose anhydrides III and IV equally promote calcium absorption from the luminally perfused rat small intestine

We examined the effects of di-D-fructose anhydride (DFA) III and IV on Ca absorption in luminally perfused segments of the small intestine in anesthetized rats. The calcium absorption rate with perfusion of 10 mmol/l CaCl2 was similarly increased by addition of 100 mmol/l DFAIII or IV, and these promotive effects of both DFAs were pronounced at perfusion rate of 0.15 ml/min than at 0.3 ml/min. The promotive effects were higher in the duodenojejunum than in the ileum.     

Age-related changes in calcium and phosphorus uptake by rat small intestine

The purpose of these experiments was to determine whether there are changes in intestinal Ca and P uptake with age and whether the regulation of Ca and P uptake changes with age. Experiments were performed in male Fischer 344 rats aged 2-3 months (young), 12-14 months (adult) and 22-24 months (old). Ca and P uptake were measured simultaneously by incubating everted intestinal sacs in a buffered salt solution containing radiolabeled 0.25 mM Ca and 1.0 mM P for 15 min. Ca uptake declined by over 50% with age in the duodenum, and P uptake showed a similar decline in both the duodenum and jejunum. The biggest decrease was seen between the young and adult age groups. These decreases in uptake were paralleled by decreases in serum 1,25-dihydroxyvitamin D with age. Administration of 1,25-dihydroxyvitamin D-3 increased Ca uptake by 50-65% in the duodenum and increased P uptake by 85-120% in the duodenum and jejunum of both young and adult rats. Although 1,25-dihydroxyvitamin D-3 increased uptake by about the same percentage in each age group, the maximal uptake was much greater in the young than in the adult. Feeding a low-Ca diet increased duodenal Ca uptake by 68% and increased serum 1,25-dihydroxyvitamin D over 2-fold in young rats. There was no significant increase in either parameter in adult rats fed a low-Ca diet. However, duodenal P uptake was stimulated by a low-Ca diet by 87% in young rats and by 51% in adult rats. These results demonstrate that there is an age-related decline in Ca and P uptake by the intestinal mucosa. In addition, there is decreased capacity of 1,25-dihydroxyvitamin D-3 and a low-Ca diet to stimulate intestinal uptake in the adult.