Intestinal bile acid absorption. Na(+)-dependent bile acid transport activity in rabbit small intestine correlates with the coexpression of an integral 93-kDa and a peripheral 14-kDa bile acid-binding membrane protein along the duodenum-ileum axis.

Kramer, Werner; Girbig, Frank; Gutjahr, Ulrike; Kowalewski, Simone; Jouvenal, Karin; Müller, Günter; Tripier, Didier; Wess, G.

doi:10.1016/s0021-9258(17)46808-6

Cited by 111 publications

(16 citation statements)

References 54 publications

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“…Brush border membrane vesicles from the ileum of male white New Zealand rabbits (4-5 kg) were prepared by the Mg 2 ϩ precipitation method and characterized by transport measurements, immunological and enzymatic methods as described previously (38,39). Plasma membrane subfractions from rat liver enriched with sinusoidal surfaces were prepared as described (40).…”

Section: Preparation Of Membrane Vesicles and Transport Measurementsmentioning

confidence: 99%

“…Uptake of radiolabeled substrates by brush border membrane vesicles was determined by the membrane-filtration method as described previously (21,39). Transport reaction was initiated by adding 10 l vesicle suspension (50 g protein) to 90 l incubation medium containing the radioactively labeled substrate at 30 Њ C. The composition of the incubation medium for measurements in the presence of a Na ϩ gradient was usually 10 m m Tris/HEPES, pH 7.4, 100 m m NaCl, 100 m m mannitol, and in the absence of Na ϩ gradient 10 m m Tris/Hepes, pH 7.4, 100 m m KCl, 100 m m mannitol.…”

Section: Preparation Of Membrane Vesicles and Transport Measurementsmentioning

confidence: 99%

“…Uptake studies with [ 3 H]taurine-conjugated bile acid analogues was performed accordingly using a concentration of 50 m (0.2 Ci/determination). The transport reaction was terminated after 60 s by addition of 1 ml ice-cold 10 m m Tris/HEPES buffer (pH 7.4)/150 m m KCl and the radioactivity remaining on the filter was measured by standard liquid-scintillation techniques (38,39). After correction for radioactivity from the medium bound to the filter in the absence of membrane vesicles and chemiluminescence, absolute solute uptake was calculated and expressed as nmol/mg protein.…”

Section: Preparation Of Membrane Vesicles and Transport Measurementsmentioning

confidence: 99%

“…After washing the membranes, SDS-PAGE was carried out in vertical slab gels (20 ϫ 17 ϫ 0.15 cm) using an electrophoresis System LE 2/4 (LKB Pharmacia Biotechnologie, Freiburg, Germany) as described (39,43). After staining with Serva Blue R 250, the gels were scanned with a densitometer CD 50 (DESAGA, Heidelberg, Germany) and the individual lanes were cut into slices of 2 mm thickness.…”

Section: Photoaffinity Labeling and Sds Pagementioning

confidence: 99%

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Substrate specificity of the ileal and the hepatic Na+/bile acid cotransporters of the rabbit. I. Transport studies with membrane vesicles and cell lines expressing the cloned transporters

Kramer¹,

Stengelin²,

Baringhaus³

et al. 1999

Journal of Lipid Research

102

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The substrate specificity of the ileal and the hepatic Na ؉ /bile acid cotransporters was determined using brush border membrane vesicles and CHO cell lines permanently expressing the Na ؉ /bile acid cotransporters from rabbit ileum or rabbit liver. The hepatic transporter showed a remarkably broad specificity for interaction with cholephilic compounds in contrast to the ileal system. The anion transport inhibitor diisothiocyanostilbene disulfonate (DIDS) is a strong inhibitor of the hepatic Na ؉ /bile acid cotransporter, but does not show any affinity to its ileal counterpart. Inhibition studies and uptake measurements with about 40 different bile acid analogues differing in the number, position, and stereochemistry of the hydroxyl groups at the steroid nucleus resulted in clear structure-activity relationships for the ileal and hepatic bile acid transporters. The affinity to the ileal and hepatic Na ؉ /bile acid cotransport systems and the uptake rates by cell lines expressing those transporters as well as rabbit ileal brush border membrane vesicles is primarily determined by the substituents on the steroid nucleus. Two hydroxy groups at position 3, 7, or 12 are optimal whereas the presence of three hydroxy groups decreased affinity. Vicinal hydroxy groups at positions 6 and 7 or a shift of the 7-hydroxy group to the 6-position significantly decreased the affinity to the ileal transporter in contrast to the hepatic system. 6-Hydroxylated bile acid derivatives are preferred substrates of the hepatic Na ؉ /bile acid cotransporter. Surprisingly, the 3 ␣ -hydroxy group being present in all natural bile acids is not essential for high affinity interaction with the ileal and the hepatic bile acid transporter. The 3 ␣ -hydroxy group seems to be necessary for optimal transport of a bile acid across the hepatocyte canalicular membrane. A modification of bile acids at the 3-position therefore conserves the bile acid character thus determining the 3-position of bile acids as the ideal position for drug targeting strategies using bile acid transport pathways.

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Section: Preparation Of Membrane Vesicles and Transport Measurementsmentioning

confidence: 99%

Section: Preparation Of Membrane Vesicles and Transport Measurementsmentioning

confidence: 99%

Section: Preparation Of Membrane Vesicles and Transport Measurementsmentioning

confidence: 99%

Section: Photoaffinity Labeling and Sds Pagementioning

confidence: 99%

See 2 more Smart Citations

Substrate specificity of the ileal and the hepatic Na+/bile acid cotransporters of the rabbit. I. Transport studies with membrane vesicles and cell lines expressing the cloned transporters

Kramer¹,

Stengelin²,

Baringhaus³

et al. 1999

Journal of Lipid Research

102

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“…However, little is known about the effect of dietary cholesterol on ASBT in rats or rabbits. Ileal lipid binding protein (ILBP) was suggested to be involved in the transport of bile acids from the ileum (21,22). However, the exact role that ILBP plays remains controversial and the effect of cholesterol feeding on ILBP has not yet been examined.…”

mentioning

confidence: 99%

Ileal bile acid transport regulates bile acid pool, synthesis, and plasma cholesterol levels differently in cholesterol-fed rats and rabbits

Bl²,

Shefer

et al. 2000

Journal of Lipid Research

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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.Therefore, although bile acid synthesis was increased via different pathways in rats and rabbits, enhanced ileal bile acid transport was critical for enlarging the bile acid pool size that exerted feedback regulation on cholesterol 7 ␣ -hydroxylase in rabbits. -Xu,

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Bile Salt Transporters

Eloranta¹,

Stieger²,

Kullak‐Ublick³

2014

Drug Transporters

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Intestinal bile acid absorption. Na(+)-dependent bile acid transport activity in rabbit small intestine correlates with the coexpression of an integral 93-kDa and a peripheral 14-kDa bile acid-binding membrane protein along the duodenum-ileum axis.

Cited by 111 publications

References 54 publications

Substrate specificity of the ileal and the hepatic Na+/bile acid cotransporters of the rabbit. I. Transport studies with membrane vesicles and cell lines expressing the cloned transporters

Substrate specificity of the ileal and the hepatic Na+/bile acid cotransporters of the rabbit. I. Transport studies with membrane vesicles and cell lines expressing the cloned transporters

Ileal bile acid transport regulates bile acid pool, synthesis, and plasma cholesterol levels differently in cholesterol-fed rats and rabbits

Bile Salt Transporters

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