Negative feedback regulation of the ileal bile acid transport system in rodents (original) (raw)
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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~
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.
Journal of Clinical Investigation, 1997
Although bile acid transport by bile duct epithelial cells, or cholangiocytes, has been postulated, the details of this process remain unclear. Thus, we performed transport studies with [ 3 H]taurocholate in confluent polarized monolayers of normal rat cholangiocytes (NRC). We observed unidirectional (i.e., apical to basolateral) Na ϩ -dependent transcellular transport of [ 3 H]taurocholate. Kinetic studies in purified vesicles derived from the apical domain of NRC disclosed saturable Na ϩ -dependent uptake of [ 3 H]taurocholate, with apparent K m and V max values of 209 Ϯ 45 M and 1.23 Ϯ 0.14 nmol/mg/10 s, respectively. Reverse transcriptase PCR (RT-PCR) using degenerate primers for both the rat liver Na ϩdependent taurocholate-cotransporting polypeptide and rat ileal apical Na ϩ -dependent bile acid transporter, designated Ntcp and ASBT, respectively, revealed a 206-bp product in NRC whose sequence was identical to the ASBT. Northern blot analysis demonstrated that the size of the ASBT transcript was identical in NRC, freshly isolated cholangiocytes, and terminal ileum. In situ RT-PCR on normal rat liver showed that the message for ASBT was present only in cholangiocytes. Immunoblots using a well-characterized antibody for the ASBT demonstrated a 48-kD protein present only in apical membranes. Indirect immunohistochemistry revealed apical localization of ASBT in cholangiocytes in normal rat liver. The data provide direct evidence that conjugated bile acids are taken up at the apical domain of cholangiocytes via the ASBT, and are consistent with the notion that cholangiocyte physiology may be directly influenced by bile acids. ( J. Clin. Invest. 1997. 100:2714-2721.) Key words: biliary epithelia • taurocholate • transport • liver • plasma membrane vesicles Preliminary portions of this work were presented at the 47th meeting of the American Association for the Study of Liver Diseases, and have been published in abstract form (1996. Hepatology. 94:897 a ).
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.
We investigated the effect of ileal bile acid transport on the regulation of classic and alternative bile acid synthesis in cholesterol-fed rats and rabbits. Bile acid pool sizes, fecal bile acid outputs (synthesis rates), and the activities of cholesterol 7 ␣ -hydroxylase (classic bile acid synthesis) and cholesterol 27-hydroxylase (alternative bile acid synthesis) were related to ileal bile acid transporter expression (ileal apical sodium-dependent bile acid transporter, ASBT). Plasma cholesterol levels rose 2.1-times in rats (98 ؎ 19 mg/dl) and 31-times (986 ؎ 188 mg/dl) in rabbits. The bile acid pool size remained constant (55 Ϯ 17 mg vs. 61 ؎ 18 mg) in rats but doubled (254 ؎ 46 to 533 ؎ 53 mg) in rabbits. ASBT protein expression did not change in rats but rose 31% ( P Ͻ 0.05) in rabbits. Fecal bile acid outputs that reflected bile acid synthesis increased 2-and 2.4-times ( P Ͻ 0.05) in cholesterol-fed rats and rabbits, respectively. Cholesterol 7 ␣ -hydroxylase activity rose 33% (24 ؎ 2.4 vs. 18 ؎ 1.6 pmol/mg/min, P Ͻ 0.01) and mRNA levels increased 50% ( P Ͻ 0.01) in rats but decreased 68% and 79%, respectively, in cholesterol-fed rabbits. Cholesterol 27-hydroxylase activity remained unchanged in rats but rose 62% ( P Ͻ 0.05) in rabbits. Classic bile acid synthesis (cholesterol 7 ␣hydroxylase) was inhibited in rabbits because an enlarged bile acid pool developed from enhanced ileal bile acid transport. In contrast, in rats, cholesterol 7 ␣ -hydroxylase was stimulated but the bile acid pool did not enlarge because ASBT did not change.
Annals of hepatology, 2017
The primary bile acids (BAs) are synthetized from colesterol in the liver, conjugated to glycine or taurine to increase their solubility, secreted into bile, concentrated in the gallbladder during fasting, and expelled in the intestine in response to dietary fat, as well as bio-transformed in the colon to the secondary BAs by the gut microbiota, reabsorbed in the ileum and colon back to the liver, and minimally lost in the feces. BAs in the intestine not only regulate the digestion and absorption of cholesterol, triglycerides, and fat-soluble vitamins, but also play a key role as signaling molecules in modulating epithelial cell proliferation, gene expression, and lipid and glucose metabolism by activating farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor-1 (GPBAR-1, also known as TGR5) in the liver, intestine, muscle and brown adipose tissue. Recent studies have revealed the metabolic pathways of FXR and GPBAR-1 involved in the biosynthesis and enterohepatic circu...
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
Bile acid excretion: the alternate pathway in the hamster
Journal of Clinical Investigation, 1977
quantitative significance of renal excretion of bile acid ester sulfates as an alternate excretory pathway was evaluated in hamsters. After bile duct ligation, total serum bile acid fell from a mean level of 454 ,g/ml at 24 h to 64 ,ug/ml by 96 h. During this period the bulk of the bile acid pool could be accounted for as esterified bile acids in urine. Renal pedicle ligation of animals with bile duict obstruction led to retention of the bile acid ester sulfates in serum. Thioacetamide hepatotoxicity diminished ester sulfation of bile acids causing diminished renal secretion with relatively greater retention of nonesterified bile acids in serum. We conclude that secretion of esterified bile acids by the kidney is an efficient alternate pathway for maintaining bile acid excretion in obstructive biliary tract disease. Coexistent hepatocellular disease diminishes ester sulfation and the effectiveness of the alternate pathway in maintaining bile acid excretion.