Effect of bile salts on transport across brush border of rabbit ileum (original) (raw)

Bile acid active and passive ileal transport in the rabbit: effect of luminal stirring

European Journal of Clinical Investigation, 1992

The intestinal absorption of bile acids (BA) with different chemical structure has been evaluated in the rabbit, after intestinal infusion of different concentrations (0.25-30 mM) of BA, by mesenteric blood sampling. Cholic (CA), chenodeoxycholic (CDCA), ursodeoxycholic (UDCA) acid, free and taurine (T-) conjugated, together with glycocholic (GCA) acid and deoxycholic acid (DCA) were studied. The apparent uptake parameters were calculated. All conjugated BA showed active transport (T max, nmol min-' cm-' int.), with Tmax values in the following order: TCA > TUDCA > TCDCA; unconjugated BA showed passive uptake, with values in the following order: DCA > CDCA > UDCA > CA. GCA and CA showed both passive uptake and active transport. For all BA studied the % uptake in the ileal segment considered was less than lo%, BA uptake being thus limited by transport and/or diffusion kinetics, rather than by flow velocity. The liquid resistance to BA radial diffusion inside the lumen was evaluated, and the infusate-to-blood uptake parameters corrected for it, in order to get the uptake parameters from the epithelium-to-liquid interface to mesenteric blood: the apparent Km decreased, passive uptake coefficient increased, while Tmax was unchanged. The passive component of the uptake, corrected for the luminal resistance, correlated with the BA hydrophobicity (r = 0.963; P < 0.01). These studies show that: (a) the active transport for BA in the rabbit ileum is mediated by a saturable, highefficiency, low-affinity carrier; (b) that passive transport is highly efficient for unconjugated BA, mainly for the most lipophilic ones; (c) that both systems are important in the intestinal absorption of BA.

Transport of bile acids in a human intestinal epithelial cell line, Caco-2

Biochimica et Biophysica Acta (BBA) - General Subjects, 1990

The transport of tanrocholic acid (TA) across Caco-2 cell monolayers was dependent on time in culture and reached a plateau after 28 days, at which time the apical (AP)-to-basolateral (131,) transport was 10-times greater than BL-to-AP transport. The amounts of TA inside the cells following application of 10 nM [I4C]TA to tile AP or BL side of the monolayers (30 min) were approximately equal (54.4 + 2.7 and 64.6 ± 2.8 fmol/mg protein, respectively). AP-to-BL transport of TA was saturable and temperature-dependent. Vm~ , and K m for transport were 13.7 pmol / mg protein per min and 49.7 pM, respectively. The transport of TA had an activation energy of 13.2 kcal-mo1-1, required Na + and glucose. AP-to-BL transport of |14C]TA was inhibited by the co-administration (on the AP side) of either unlabeled TA or deoxycholate, but it was not reduced by the presence of unlabeled TA on the BL side.

BILE-ACIDS REVERSIBLE EFFECTS ON SMALL INTESTINAL PERMEABILITY - AN INVITRO STUDY IN THE RABBIT

Digestive Diseases and Sciences, 1990

To define the action of deconjugated bile acids on the small intestinal permeability in an in vitro system, we investigated the effects of chenodeoxycholic acid and ursodeoxycholic acid on the rate of transmural flux of lactulose in jejunal and ileal mucosa of rabbits, stripped of their muscle layers and mounted in Ussing chambers. In a series of experiments, tissue samples from small intestinal segments either exposed to bile acids or not also were examined by scanning and transmission electron microscopy to study the integrity of the tight junctions. Results show that chenodeoxycholate, starting at the concentration of 0.1 mM, enhanced in a dose-related manner the transepithelial flux of lactulose in the ileum. Both chenodeoxycholate (0.5 mM) and ursodeoxycholate (0.5 mM) significantly increased mucosal permeability to lactulose in jejunum and ileum; the effect of chenodeoxycholate was also shown to be reversible, as it completely disappeared within 40 min after its withdrawal and it did not result in permanent changes of epithelial transport function. Finally, the tight junctions appeared loosened by the addition of 1 mM chenodeoxycholate, suggesting that this is the major site of the transient bile acid increase of small intestinal permeability to compounds such as lactulose, having a molecular radius wider than 0.5 nm.

Development of active and passive transport of bile acids in rabbit intestine

Mechanisms of Ageing and Development, 1987

Previous studies have indicated that saturable, N absent in the ileum throughout most of the suckling t ileal bile acid uptake which occurs during weaning resl in functional bile acid carriers within the ileal brush 1 undertaken in weanling and adult rabbits to establish active ileal and passive jejunal and colonic uptake of 8 a range of concentrations of cholic (C), taurocholic (T(cholic (CDC), tauroehenodeoxycholic (TCDC), glychoc cholic (I)C) and taurodeoxycholic (TI)C) acid was detl TC, GC, DC and TI)C was greater in adult than in we~)rhea and mat me maturatac results primarily through an inc border membrane. This stud~ establish the effect of maturation ol bile acids. The in vitro upta (TC), glycocholic (GC), chenod¢ rchochenodeoxycholic (GCI)C), de determined. Active ileal uptake ruling animals, whereas uptaJ was similar in both groups. The relative permeability for p~ o the jejunum and colon was similar in young and adult rat area was similar in the two groups, but was greater in the i ,' weanling rabbits due to an increase in villus height, width serosal length. However, the age-associated differences in a not explained simply on the basis of these differences in • the concentration of bile acids in the intestinal lumen, q }it from weanling to adulthood does not influence the rel the jejunum or colon to bile acids, but does increase active td unconjugated cholic acid and deoxycholic acid, but not c[ 1; Aging; Bile acids; Colon; Ileum; Jejunum; Ontogeny; P~

Colonic absorption of unconjugated bile acids

Digestive Diseases and Sciences, 1979

Colonic absorption of three major unconjugated bile acids-cholate, chenodeoxycholate, and deoxycholate-was measured under steady-state conditions using a technique of co-Ionic perfusion in healthy volunleers. Aqueous solutions at pH 8.0 and varying in concentration from 1 mM to 10 mM were used. The rate of chenodeoxycholate absorption averaged nine times that of cholate absorption; deoxycholate absorption was somewhat less than that of chenodeoxycholate absorption, averaging six times that of cholate. At concentrations below 5 mM, the rate of absorption of bile acids was directly proportional to concentration, so that "clearance" could be calculated. Clearance values for a 1-mM solution (ml/min/colon, mean +_ SE) were: chenodeoxycholate, 9.84 +_ 1.0; deoxycholate, 7.0 +-1; and cholate, 0.82 +_ 0.10. Since absorption was proportional to concentration in the lumen, and was more rapid for the dihydroxy acids, the major mechanism of absorption was thought to be passive nonionic diffusion. Maximal rates of bile acid absorption were calculated from a l-mM solution and found to be as high as 4.2 g/day for chenodeoxycholate, 3.2 g/day for deoxycholate, and 0.5 g/day for cholate, and the rate would be still greater for more concentrated solutions. Colonic absorption may contribute significantly to conservation of the dihydroxy bile acid pool, especially in conditions of bile acid malabsorption. Bile acids secreted into the proximal intestine are conserved efficiently by active absorption in the ileum (2-5) augmented by passive absorption throughout the intestine (5-10). Previous experiments in man have quantitated passive bile acid absorption in the jejunum (8-10) and ileum (i0, 11) and have also provided evidence that bile acids can be absorbed from the colon (12, 13). To date, there

Effect of Bile Salts on Gastric Emptying and Intestinal Transit in the Rat

Gastroenterology, 1968

Although much work has been done on the effects of bile salts on gastric and intestinal motility,l-7 there have been few reports of the effects of bile salts on gastric emptying and intestinal transit. 6 ,7 Studies, presently being conducted in our laboratory on the effect of orally administered bile salts on drug absorption, have led to a consideration of the influence of bile salts on gastric emptying and intestinal transit rates. The absorption of many drugs depends upon their presence in specific areas of the gastrointestinal tract. An increase or delay in gastric emptying or intestina l transit could markedly affect the absorption characteristics of these drugs. The following study was designed to investigate these areas. Materials and Methods 1Vlaterials. Sodium taurodeoxycholate was obtained from Maybridge Chemical Company, Ltd., North Cornwall, United Kingdom. It was chromatographically pure. Sodium deoxycholate (special enzyme grade) was obtained from Mann Research Laboratories, Inc., New York, New York. Methods. Male Sprague-Dawley descent rats (Blue Spruce Farms, Altamont, New York) weighing between 130 and 180 g were fasted for 24 hr prior to the experiment. Water was allowed ad libitum. One and one-half milliliters of a 0.07% phenol red solution (prewarmed to 35 to 37 C),

Transport of drugs in isolated hepatocytes the influence of bile salts

Biochemical Pharmacology, 1978

The influence of bile salts on hepatic transport of drugs was studied using isolated hepatocyte suspensions. Upra~e of the organic anions, dibromosulphthalein (DBSP), indcrcyanine green (ICG) and an organic cation, N4-acetyi procainamide ethobromide (APAEB) was measured. Afte; 60 min incubation the amount of DBSP, ICG and APAEB nresent in the cells was 17. 41 and 4.5 ner cent of the added amount respectively. The release of DBSP, ICG and APAEB from the hepatocytes preincubated with the agents under study, after 60 min incubation in fresh medium was 80.5, 12.5 and 48.9 per cent of the amount initially present respectively. The presence of bile canalicular membranes in the isolated hepatocytes was demonstrated by enzymehistochemistry: 5'nucleotidase activity showed sharp branched bands over the cell surface. When bile salts were present in the incubation medium. the cellular content of DBSP, ICG and APAEB was diminished. The taurocholate concentration which caused 50 per cent of the maximal effect was 0.07mM. O.lOmM and 0.06mM in experiments with DBSP, ICG and APAEB respectively. Pharmacokinetic analysis revealed that the influence of bile salts on cellular content of the three compounds was due to inhibition of the uptake into the isolated hepatocytes, rather than stimulation of release from the cells. The hypothesis, that stimulation of biliary output of organic anions in viw is due to a modifying effect of bile salts on the canalicular membranes. instead of being the result of the increased bile flow, is not supported by this study.

Bile acids reversible effects on small intestinal permeability

Digestive Diseases and Sciences, 1990

Effect of bile salts on transport across brush border of rabbit ileum (original) (raw)

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