Jejunum is more important than terminal ileum for taurocholate absorption in rats

The terminal ileum, with its active transport system, is considered the major site of bile salt absorption. However, earlier studies used bile salt concentrations below physiological levels and may not apply in vivo. Analysis of these studies shows that ileal active transport cannot account for total bile salt recovery. To reevaluate bile salt absorption in rats, we used four preparations and physiological bile salt concentrations. Studies with intestinal sacs showed that, above critical micellar concentration, uptake of taurocholate (TC) was equal in both jejunum and ileum and linear with respect to concentration. A similar pattern was observed in studies of mucosal-to-serosal TC transport using a flux chamber. In vivo studies in anesthetized rats showed approximately 30% of TC absorbed from proximal jejunum and appearing in bile when the bolus had traversed only half the intestine. In unanesthetized fed rats, 60% of TC appeared in bile before the bolus reached distal ileum. Because luminal concentrations of TC are highest proximally, passive absorption by the proximal intestine is mainly responsible for conserving TC within the enterohepatic circulation. Ileal active transport is more efficient at low concentrations and absorbs the TC remaining after proximal absorption.     

Ion transport by rabbit jejunum in vivo.

Net ion and H2O transport by jejunum adjacent to the ligament of Treitz (proximal jejunum) and midjejunum were measured in vivo by continuous perfusion with HCO3-Ringer solution containing a volume marker. Proximal jejunum secreted Na and H2O, whereas midjejunum absorbed Na and H2O. Both segments secreted CO2 and absorbed K and Cl. D-glucose stimulated absorption of Na and H2O and the transmural electrical potential difference (PD) in both segments, but these changes were not accompanied by alterations in Cl, CO2, or K fluxes. However, the increse in Na absorption caused by 3-O-methylglucose was matched by an increase in Cl absorption. This, in addition to increased tissue lactate concentration after addition of D-glucose, suggests that organic anion maintains electroneutrality for Na transport enhanced by D-glucose. Cholera toxin had no effect on ion transport or PD in proximal jejunum, but cholera toxin stimulated secretion and increased the PD in more distal jejunum. Although proximal jejunum shows spontaneous secretory activity, its capacity for secretion is not as great as more distal small intestine.     

The effects of bile salt and raw bile on the intestinal absorption of micellar fatty acid in the rat in vitro

1. The uptake, esterification and transport of [(14)C]oleic acid were studied using sacs of rat everted small intestine incubated in 25 ml. of a buffered mixture of sodium taurocholate, glyceryl mono-oleate and (14)C-labelled oleic acid in micellar form.2. Intestine obtained from bile fistula rats (bile duct cannulated 48 hr previously) showed elevated rates of (14)C uptake into the tissue total lipid compared with sham-operated controls.3. Nearly all of the excess (14)C uptake in the bile fistula group was in the form of free fatty acid. Both groups showed similar rates of [(14)C]oleic acid incorporation into tissue triglyceride and also similar, though small, amounts transported into the serosal fluid.4. In further experiments using intestine from bile fistula rats the addition of 1 ml. of fresh rat bile to the incubation mixture reduced the (14)C uptake to approximately control levels. The addition of 2-3 ml. of fresh bile similarly reduced the uptake and increased (14)C incorporation into the triglycerides of mucosal tissue and serosal fluid.5. These responses were not entirely the result of the bile salts contained in fresh bile since increasing the taurocholate concentration per se caused uptake, esterification and transport all to increase. In the presence of the higher taurocholate concentration the addition of fresh bile still caused a decrease in (14)C uptake.6. There was no significant effect of either fresh bile or taurocholate on the transport of the 3-O-methyl analogue of D-glucose under comparable conditions.7. It is concluded that raw bile contains one or more components other than bile salts which may be important in determining fatty acid absorption.     

A scanning electron microscope study on the effects of different bile salts on the epithelial lining of jejunal mucosa

Deconjugation of bile salts may occur in the jejunum under conditions of bacterial proliferation in the upper small intestine. We studied the morphological changes of jejunal mucosa induced by different conjugated (taurocholate, taurodeoxycholate, taurochenodeoxycholate, tauroursodeoxycholate) and unconjugated (cholate, deoxycholate, chenodeoxycholate, ursodeoxycholate) bile salts as compared by scanning electron microscopy. The epithelial lining of the jejunum was not affected in structural appearance below 40 mM concentration of the conjugated bile salts examined. On the other hand, the unconjugated bile salts examined induced morphological changes in varying degree and severity from crack formation at the tip to complete denudation of the jejunal villi, depending on the kind and dose of bile salts given. Among the unconjugated bile salts examined, the most robust in action was deoxycholate, which induced crack formation at 1.0 mM concentration, and the weakest was cholate. The study suggests that deconjugated bile salts produced by bacterial overgrowth in the upper small intestine can induce breakdown of the junctional integrity of the epithelial lining in varying degree and severity, ultimately leading to exfoliation of the epithelium.     

The effect of fasting on hexose transfer in rat intestine

1. A technique has been developed whereby accurately defined segments of rat intestine can be isolated in vivo, and this technique was used to study the influence of fasting on hexose transport.2. In the distal ileum the transport of glucose and galactose was stimulated by fasting. The effect was specific as neither amino acid transport nor the permeability of the luminal membrane of the absorbing epithelium was altered by fasting. The increased hexose transport was accompanied by a reduced accumulation of hexose in the gut wall. In the proximal jejunum hexose transport was not stimulated by fasting.3. The results of in vitro experiments show the relative importance of hexose metabolism in providing energy for transport in different regions of the small intestine in both fed and fasted animals. In conditions where hexose metabolism was reduced, e.g. by fluoride, the proximal jejunum behaved more like the distal ileum and a stimulation of hexose transport in response to fasting was demonstrable in vivo.4. Motility studies showed that phenol red introduced into the stomach reached the ileum sooner, achieved a higher concentration and remained there for a longer period of time in the fasted animal.5. The changes in carbohydrate metabolism, hexose transport capacity and gastrointestinal motility are discussed in relation to adaptations of the rat to fasting.     

The site and characteristics of intestinal water and electrolyte loss in Escherichia coli-induced diarrhoea in calves

Diarrhoea was induced in neonatal calves by the oral administration of an enteropathogenic strain of Escherichia coli. The calves were protected by IgM against septicaemia. Under anaesthesia, movements of water and electrolytes were measured at four points in the small intestine and at one point in the proximal spiral colon. The results were compared with those from healthy control animals.Control animals showed net secretion of sodium and chloride in the upper jejunum changing progressively to net absorption in the distal ileum. Bicarbonate was absorbed in the proximal and secreted in the distal small intestine, and potassium was secreted at all points examined.In the diarrhoeic animals there were increased net losses of water, sodium, potassium and chloride in the distal small intestine, whereas the spiral colon of these animals showed significantly greater net absorption of water and sodium than did the controls. However, potassium losses in the colon were greater in the diarrhoeic calves. No significant difference in net bicarbonate movement could be shown between the two groups.Unidirectional fluxes of water and sodium were significantly reduced throughout the intestine in the diarrhoeic animals compared with the controls.It was concluded that the distal small intestine was the main site of net loss of water and electrolytes, but that there was partial compensation by the proximal spiral colon for losses of water and sodium. This may have been mediated by aldosterone.     

Comparative effects of sodium taurodeoxycholate and sodium taurocholate on bile secretion in the rat, dog and rabbit.

1. The biliary effects of sodium taurodeoxycholate and sodium taurochloate were investigated in anaesthetized dogs and rats, and in the isolated perfused rat liver. 2. Both bile salts had similar qualitative and quantitative effects on the flow and composition of bile in the dog. 3. In the rat, the bile salts had similar effects on the ionic compoistion of bile, but differed in that bile flow was not always directly related to the rate of bile salt secretion in bile, in the experiments with sodium taurodeoxycholate. 4. Sodium taurodeoxycholate is hydroxylated form sodium taurocholate by the liver of the rat but not by that of the dog. 5.The biliary effects of sodium taurodexoycholate in the rat and in the dog are contrasted with its effects in the rabbit, and the differences between the three species are discussed.     

Hexose transport across the apical and basolateral membrane of enterocytes from different regions of the chicken intestine

The properties of hexose transport across the apical and basolateral membranes of chicken enterocytes have been studied in the small and large intestine. Results show that (a) isolated epithelial cells from all segments except the coprodeum can accumulate 3-O-methylglucose (Glc3Me) against a concentration gradient, by a Na⁺-dependent and phloridzin-sensitive mechanism, (b) The cell cumulative capacity for Glc3Me (control/phloridzin-incubated cells) is lower in the small intestine than in the large intestine (rectum = proximal caecum = ileum > jejunum > duodenum). (c) Theophylline enhances the cell Glc3Me cumulative capacity 2.9-fold in the duodenum and 2.4-fold in the jejunum but has no effect in the other segments studied. (d) Analysis of sugar uptake indicates that net hexose influx rates decrease from proximal to distal regions: jejunum > duodenum > ileum = proximal caecum = rectum for the apical transport system (-methyl glucoside as substrate and phloridzin as inhibitor) and duodenum > jejunum > ileum = proximal caecum = rectum for the basolateral system (2-deoxyglucose; theophylline). (e) The duodenum and the jejunum show high apical and basolateral hexose transport rates, which confer a significant capacity for sugar absorption on the proximal intestine. More distal regions, including the ileum, the proximal caecum and the rectum, have transport systems analogous to those of the proximal intestine that keep a considerable potential capability to recover hexoses from the lumen.     

Influence of Eimeria acervulina duodenal coccidiosis on intestinal absorption of lysine and on the movement of water and electrolytes

The absorption rate of 14C L-lysine and net flux of water and mineral ions (Na+, K+) were studied in 4-week-old male chickens infected with Eimeria acervulina (10(6) sporulated oocysts/chicken). Intestinal coccidiosis significantly decreased absorption rate of 14C-lysine. This effect was particularly pronounced in the jejunum. Net flux of water was also modified: its absorption was decreased in the middle and distal small intestine. In the duodenum a net absorption of water was converted to a net excretion. These effects were accompanied by an increase in tissue water content and in secretion rate of Na+ and K+.     

Bile salt and non-bile salt components in bile affecting micellar cholesterol uptake by rat intestine in vitro

1. The uptake of micellar cholesterol was measured in sacs of the upper half of everted rat intestine. Sacs of 20 cm length were incubated 1 hr in 25 ml. phosphate buffer containing fatty acid, monoglyceride and (3)H-labelled cholesterol in micellar form with the bile salt, sodium taurocholate, as the dispersing agent.2. Sacs obtained from bile fistula rats (bile duct cannulated 48 hr previously) took up more than twice as much cholesterol as did sacs obtained from untreated control rats.3. In experiments utilizing bile-deficient sacs increasing the sodium taurocholate concentration caused an increase in cholesterol uptake. Conversely, adding a small amount of whole bile caused a decrease in cholesterol uptake.4. The inhibitory effects of the bile were greatly enhanced if the bile was pre-treated with cholestyramine to remove the bile salts.5. It is concluded that bile has a variable effect on intestinal cholesterol absorption depending upon its relative concentration of bile salt and a non-bile salt component having opposite actions.6. It is suggested that the variable effect may be related to the physico-chemical dispersion of cholesterol and that the non-bile salt component may be lecithin.     

Bile salt-associated electrolyte secretion. A study following a short-term biliary obstruction in the rat.

The mechanisms involved in bile salt-induced choleresis are poorly known. To give an insight in this physiological process, bile salt-associated electrolyte secretion was studied following relief of a short-term (2h) biliary obstruction in the rat, an experimental model that shows an important diminution of bile salt choleretic efficiency. For this purpose, biliary excretion of total bile salts and electrolytes (sodium, chloride and bicarbonate) were studied in such a model during taurocholate infusion at increasing rates. The results showed that bile flow, bile salt output and electrolyte secretion stimulated by taurocholate administration were decreased in the rats that were subjected to biliary obstruction. Besides, the choleretic efficiency of the excreted bile salts, as estimated by the slope of the regression line of bile flow vs. bile salt output, was diminished by 46% (p < 0.005). Multiple regression analysis of bile flow vs. bile salt and electrolyte outputs allowed to detect a selective diminution of the fraction of bile flow related to bile salt-associated electrolyte secretion ("secretory fraction" of the choleretic efficiency of bile salts) (3.2 +/- 0.3 vs. 2.5 +/- 0.2 L/mol, p < 0.05) whereas the "osmotic fraction" of the choleretic efficiency of bile salts was not modified by the treatment (5.0 +/- 0.4 vs. 5.1 +/- 0.3 L/mol, p > 0.05). Since both chloride and bicarbonate biliary concentrations in the volume of bile stimulated by taurocholate were reduced by 53% and 52% respectively, a role of these anions in the generation of bile salt-induced choleresis was suggested. Possible mechanisms involved in such a process and in its early impairment during cholestasis are discussed.     

Villous tissue osmolality and intestinal transport of water and electrolytes

The villous tissue hyperosmolality created by the intestinal countercurrent multiplier has been proposed to be of importance for fluid transport across the intestinal epithelium in vivo. This study was performed to test this hypothesis. Net transport of fluid and electrolytes (sodium, potassium and chloride), as well as unidirectional fluxes of water and sodium were determined in the small intestine of the cat. The villous osmolality was altered by varying the composition of sodium and glucose in the isotonic solutions perfusing the intestinal lumen. Net transport of fluid was correlated to tissue osmolality mainly due to an increase of the unidirectional flux of water from lumen to tissue with augmented tissue osmolality. The results are thus consistent with the view that the intestinal countercurrent multiplier is of essential importance for net water transport. A correlation was found between net water and net sodium intestinal transport. A similar correlation was also demonstrated between net sodium and net chloride absorption rates in the jejunum while in the ileum net loss of sodium into the intestinal lumen was not accompanied by any corresponding loss of chloride ions. This observation suggests the presence of a sodium independent transport mechanism for chloride in the ilium but not in the jejunum.     

Intestinal phosphate absorption and the effect of vitamin D: a comparison of rats with mice

Previously, it was thought that intestinal phosphate transport occurred exclusively in the proximal small intestine of rodents and humans. However, a recent study has demonstrated that the ileum of mice contributes significantly to the absorption of dietary phosphate, but it is not known whether this region is also an important site of phosphate absorption in the rat. In the present study, we have investigated the mRNA and protein levels of the sodium-phosphate cotransporter, NaPi-IIb, in three regions of rat and mouse small intestine, and related its expression levels to the rate of net phosphate absorption, as measured using the in situ intestinal loop technique. 1,25-Dihydroxyvitamin D3 is an important physiological regulator of intestinal phosphate absorption that increases phosphate transport in both the duodenum and jejunum of the rat. Based on the recently proposed regional profile of phosphate absorption along the mouse small intestine, we have re-evaluated the effects of 1,25-dihydroxyvitamin D3 using three distinct regions of the mouse and rat small intestine. Our studies have revealed important differences in the intestinal handling of phosphate between mice and rats. In mice, maximal phosphate absorption occurs in the ileum, which is paralleled by the highest expression levels of NaPi-IIb mRNA and protein. In contrast, in rats maximal absorption occurs in the duodenum with very little absorption occurring in the ileum, which is similar to the pattern reported in humans. However, in both rodent species only the jejunum shows an increase in phosphate absorption in response to treatment with 1,25-dihydroxyvitamin D3.     

The effect of glycine-conjugated bile acids on net transport and potential difference across isolated rat jejunum and ileum

1. Five mM glycodeoxycholate and glycochenodeoxycholate inhibit net fluid transport across isolated rat jejunum and ileum; 5 mM glycocholate does not affect jejunal segments, but arrests fluid transport across ileal segments.2. Inhibition of fluid transport is accompanied by some diminution of mucosal glucose uptake, but translocation of glucose to the serosal surface of jejunal segments persists in the presence of dihydroxy conjugated bile acids.3. Inhibition of fluid transport is accompanied by a marked fall in the glucose-stimulated transmural electropotential difference, within 5 min of mucosal exposure to the bile acids.4. The lactate concentration gradient normally maintained across isolated intestine is abolished when fluid transport is inhibited by conjugated bile acids, even though lactate formation is not greatly reduced.5. These results suggest that inhibition of intestinal fluid transport is reproducible in vitro, and that the inhibition is not associated with increased permeability of the mucosa, but may be associated with altered permeability of the mucosal pole of the enterocyte.6. Although in vitro and in vivo effects of dihydroxy bile acids on fluid transport are similar, the assumption that the mode of action is likewise similar is not justified on present evidence.     

Relationship between volatile fatty acids and magnesium absorption in mono- and polygastric species.

In monogastric animals magnesium is absorbed from the small and large intestine. In ruminants the forestomach system, in particular the rumen, is the most important site of magnesium absorption. Various mechanisms are involved in intestinal magnesium absorption (solvent drag, diffusion, carrier-mediated transport). In the large intestine and rumen an active transepithelial magnesium transport from the mucosal to the serosal side of the epithelium was recently demonstrated. Since in the large intestine and in the rumen, volatile fatty acids (VFA, mainly acetate, propionate, butyrate) deriving from fermentation of carbohydrates represent the major anions, the influence of VFA on magnesium absorption from these parts of the gut was recently investigated. VFA at physiological concentrations stimulated magnesium absorption in both cases. In the rat large intestine VFA enhanced only magnesium absorption by the distal colon, sodium and water absorption remaining unaffected. Both in sheep rumen and in the distal colon of the rat butyrate was most effective in this regard, followed in descending order by propionate and acetate. Sodium absorption by the rat proximal colon and caecum, and by the sheep rumen, was similarly enhanced by VFA. It has been suggested that the latter effect is due to the function of VFA as intracellular proton donators for the Na+/H+ exchanger located in the apical membrane of the epithelial cells. In analogy a Mg2+/H+ exchanger, located in the apical membrane of the epithelium in the distal colon and rumen, is fully consistent with the stimulatory effects of VFA on magnesium absorption at these sites.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of taurocholate, taurochenodeoxycholate, and taurodehydrocholate on sulfobromophthalein transport into bile.

To test the hypothesis that incorporation of sulfobromophthalein (BSP) into mixed micelles could account for the increase in its biliary transport maximum (Tmax) by bile salts, we have compared in hamsters the influence on BSP Tmax of taurocholate and taurochenodeoxycholate (two micelle-forming physiological bile salts) to that of taurodehydrocholate, a bile salt which, in vitro, does not form micelles. In a first series of experiments, it was observed that taurocholate and taurochenodeoxycholate increased the secretion of phospholipid (40 and 53%, respectively), and cholesterol (50 and 110%, respectively), whereas taurodehydrocholate decreased the secretion of phospholipid (-31%) and cholesterol (-43%). This result suggests that, in vivo, taurodehydrocholate or its metabolites do not form mixed micelles. In a second series of experiments, it was seen that the three bile salts induced a similar increase in BSP Tmax (63% with taurocholate, 52% with taurochenodeoxycholate, and 51% with taurodehydrocholate). These results provide circumstantial evidence for the hypothesis that mixed micelle formation is not an important determinant of maximal BSP secretion into bile.     

Effect of Vilon and Epithalon on glucose and glycine absorption in various regions of small intestine in aged rats

Vilon (Lys-Glu) and Epithalon (Ala-Glu-Asp-Gly) administered orally for 1 month improved transport characteristics of the small intestine in aged rats. Vilon enhanced passive glucose accumulation in the serous fluid in inverted sac made from the distal region of the small intestine, while Epithalon enhanced this process in the medial region. Vilon stimulated active glucose accumulation in the serous sac of the medial small intestine, Epithalon - in the proximal and distal small intestinal segments. Glycine absorption increased only in the proximal intestinal segment under the effect of Epithalon.     

Recirculation and reutilization of micellar bile lecithin.

Bile lecithins, solubilized in micellar bile salt and radiolabeled in the 1-acyl fatty acid, phosphorus, and choline positions, were infused in the small bowel of fasted rats. Absorption of each label was virtually complete after 24 h. However, these lecithins were extensively hydrolyzed in the bowel lumen as well as after absorption, and neither the fatty acid nor phosphorus was significantly retained in the enterohepatic circulation or reutilized for biliary lecithin synthesis. In contrast, while choline was also dissociated from absorbed lecithin, choline was instead retained in the liver, reincorporated into newly synthesized hepatic lecithin, and sercreted in biliary lecithin in 10-fold greater amounts than either the fatty acid or phosphorus. However, the extent of choline incorporation into bile lecithin was limited and was not further increased when free choline was directly injected into the portal vein. The data therefore suggest that although only choline of absorbed lecithin is retained in the enterohepatic circulation and preserved for new biliary lecithin synthesis, exogenous choline utilization is regulated by the size of the available hepatic pool.     

Metabolic energy dependence of glucose, water and sodium absorption in the presence and absence of 'downhill' sodium gradients across isolated rat small intestine.

1. Absorption of glucose and water was studied in isolated perfused rat small intestine with arterial infusion under normal conditions and with a 'downhill' sodium gradient across the mucosa. 2. The effects of metabolic inhibitors, iodoacetate phenformin and dinitrophenol, on absorption were determined in the presence of normal and 'downhill' sodium gradients. 3. Glucose absorption was inhibited by each inhibitor, and the inhibition was independent of the direction of the sodium gradient. 4. Net sodium flux across the mucosa was also inhibited under 'downhill' sodium gradient conditions. 5. The simultaneous and parallel inhibition of both glucose and sodium transport is consistent with, but does not prove, the sodium gradient theory.