scholarly journals 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

1999 ◽  
Vol 40 (9) ◽  
pp. 1604-1617 ◽  
Author(s):  
Werner Kramer ◽  
Siegfried Stengelin ◽  
Karl-Heinz Baringhaus ◽  
Alfons Enhsen ◽  
Hubert Heuer ◽  
...  
Keyword(s):  
Bile Acid ◽  
Substrate Specificity ◽  
Cell Lines ◽  
Membrane Vesicles ◽  
Transport Studies

Mechanism by which cAMP activates PI3-kinase and increases bile acid secretion in WIF-B9 cells

2002 ◽  
Vol 283 (6) ◽  
pp. C1655-C1666 ◽  
Author(s):  
Tatehiro Kagawa ◽  
Lyuba Varticovski ◽  
Yoshimichi Sai ◽  
Irwin M. Arias
Keyword(s):  
Bile Acid ◽  
Acid Secretion ◽  
Cell Lines ◽  
Membrane Vesicles ◽  
Fluorescein Isothiocyanate ◽  
Dominant Negative ◽  
Independent Manner ◽  
Canalicular Membrane ◽  
Bile Acid Secretion ◽  
K Activity

Previous studies in rat bile canalicular membrane vesicles and WIF-B9 cells revealed that cAMP-induced trafficking of ATP-binding cassette (ABC) transporters to the canalicular membrane and their activation require phosphoinositide 3-kinase (PI3-K) products. In the present studies, canalicular secretion of fluorescein isothiocyanate-glycocholate in WIF-B9 cells was increased by cAMP and a decapeptide that enhances PI3-K activity; these effects were inhibited by wortmannin. To determine the mechanism(s) whereby cAMP activates PI3-K, we examined signal transduction pathways in WIF-B9 and COS-7 cells. cAMP activated PI3-K in both cell lines in a phosphotyrosine-independent manner. PI3-K activity increased in association with p110β in both cell lines. The effect of cAMP was KT-5720 sensitive, suggesting involvement of protein kinase A. Expression of a dominant-negative β-adrenergic receptor kinase COOH terminus (β-ARKct), which blocks Gβγ signaling, decreased PI3-K activation in both cell lines. cAMP increased GTP-bound Ras in COS-7 but not WIF-B9 cells. Expression of dominant-negative Ras abolished cAMP-mediated PI3-K, which suggests that the effect is downstream of Ras and Gβγ. These data indicate that cAMP activates PI3-K in a cell type-specific manner and provide insight regarding mechanisms of PI3-K activation required for bile acid secretion.

Substrate Specificity of Sugar Transport by Rabbit SGLT1:  Single-Molecule Atomic Force Microscopy versus Transport Studies†

Biochemistry ◽  
2007 ◽  
Vol 46 (10) ◽  
pp. 2797-2804 ◽  
Author(s):  
Theeraporn Puntheeranurak ◽  
Barbara Wimmer ◽  
Francisco Castaneda ◽  
Hermann J. Gruber ◽  
Peter Hinterdorfer ◽  
...  
Keyword(s):  
Atomic Force Microscopy ◽  
Substrate Specificity ◽  
Single Molecule ◽  
Sugar Transport ◽  
Force Microscopy ◽  
Atomic Force ◽  
Transport Studies

Transport Studies in Bacterial Membrane Vesicles

Science ◽  
1974 ◽  
Vol 186 (4167) ◽  
pp. 882-892 ◽  
Author(s):  
H. R. Kaback
Keyword(s):  
Membrane Vesicles ◽  
Bacterial Membrane ◽  
Transport Studies

Bile acid transport by basal membrane vesicles of human term placental trophoblast

1990 ◽  
Vol 99 (5) ◽  
pp. 1431-1438 ◽  
Author(s):  
Jose J.G. Marin ◽  
Maria A. Serrano ◽  
Mohamad Y. El-Mir ◽  
Nelida Eleno ◽  
C.A.Richard Boyd
Keyword(s):  
Bile Acid ◽  
Membrane Vesicles ◽  
Basal Membrane ◽  
Acid Transport ◽  
Bile Acid Transport

Comparative analysis of the ontogeny of a sodium-dependent bile acid transporter in rat kidney and ileum

1996 ◽  
Vol 271 (2) ◽  
pp. G377-G385 ◽  
Author(s):  
D. M. Christie ◽  
P. A. Dawson ◽  
S. Thevananther ◽  
B. L. Shneider
Keyword(s):  
Bile Acid ◽  
Rat Kidney ◽  
Membrane Vesicles ◽  
Mrna Levels ◽  
Sodium Dependent ◽  
Bile Acid Transporter ◽  
Old Rats ◽  
Acid Transporter ◽  
The Difference ◽  
And Function

An apical sodium-dependent bile acid transporter (ASBT) has recently been cloned and characterized in the rat ileum. Northern and Western blotting revealed both the ASBT mRNA and protein in rat kidney. The coding sequence of the kidney transcript was found to be identical to the previously cloned ileal ASBT. Indirect immunofluorescence studies localized the ASBT protein to the apical membrane of the renal proximal convoluted tubule. Kinetic analysis of sodium-dependent taurocholate uptake using membrane vesicles revealed a similar Michaelis-Menten constant value for taurocholate in the kidney and intestine. ASBT protein and function were present in the kidney but not the ileum from 7-day-old rats. On postnatal day 7, there was a sevenfold increase in ASBT steady-state mRNA levels in the kidney relative to the ileum, yet nuclear run-on assays revealed that the nascent transcription rates at this age were virtually the same. This suggests that the difference in the neonatal expression of the ASBT gene in the kidney and ileum may be in part due to differences in mRNA stability.

Transport of L-proline by luminal membrane vesicles from pars recta of rabbit proximal tubule

1988 ◽  
Vol 254 (5) ◽  
pp. F628-F633
Author(s):  
H. Roigaard-Petersen ◽  
C. Jacobsen ◽  
M. I. Sheikh
Keyword(s):  
Active Site ◽  
Membrane Vesicles ◽  
Rabbit Kidney ◽  
Renal Transport ◽  
High Affinity ◽  
Luminal Membrane ◽  
Transport Studies ◽  
Straight Tubules ◽  
Pars Recta ◽  
Maximal Capacity

The mechanism of renal transport of L-proline by luminal membrane vesicles prepared from proximal straight tubules (pars recta) of rabbit kidney was investigated. The following picture emerges from transport studies: an electrogenic and Na+-requiring system confined to this region of nephron exists for transport of L-proline with a high affinity (Km = 0.16 mM) and low capacity (Vmax = 3.5 nmol.mg protein-1.15 S-1). Lowering the pH from 7.5 to 5.5 increased the affinity (Km lowered from 0.16 mM at pH 7.5 to 0.08 mM at pH 5.5) without changing the maximal capacity of this system. Modification of histidyl residues of the intact luminal membrane vesicles by diethyl-pyrocarbonate (DEP) completely abolished the transient renal accumulation of L-proline. Simultaneous presence of Na+ and L-proline (10 mM) protects against DEP inactivation of renal transport of radioactive L-proline. We propose that a histidyl residue may be at or close to the active site of L-proline transporter in vesicles from the pars recta.

scholarly journals Evaluating Hepatobiliary Transport with 18F-Labeled Bile Acids: The Effect of Radiolabel Position and Bile Acid Structure on Radiosynthesis and In Vitro and In Vivo Performance

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Stef De Lombaerde ◽  
Ken Kersemans ◽  
Sara Neyt ◽  
Jeroen Verhoeven ◽  
Christian Vanhove ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Membrane Vesicles ◽  
Hepatic Uptake ◽  
Hepatobiliary Transport ◽  
Bile Acid Transporters ◽  
Significant Difference ◽  
The Impact

Introduction. An in vivo determination of bile acid hepatobiliary transport efficiency can be of use in liver disease and preclinical drug development. Given the increased interest in bile acid Positron Emission Tomography- (PET-) imaging, a further understanding of the impact of 18-fluorine substitution on bile acid handling in vitro and in vivo can be of significance. Methods. A number of bile acid analogues were conceived for nucleophilic substitution with [18F]fluoride: cholic acid analogues of which the 3-, 7-, or 12-OH function is substituted with a fluorine atom (3α-[18F]FCA; 7β-[18F]FCA; 12β-[18F]FCA); a glycocholic and chenodeoxycholic acid analogue, substituted on the 3-position (3β-[18F]FGCA and 3β-[18F]FCDCA, resp.). Uptake by the bile acid transporters NTCP and OATP1B1 was evaluated with competition assays in transfected CHO and HEK cell lines and efflux by BSEP in membrane vesicles. PET-scans with the tracers were performed in wild-type mice (n=3 per group): hepatobiliary transport was monitored and compared to a reference tracer, namely, 3β-[18F]FCA. Results. Compounds 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA were synthesized in moderate radiochemical yields (4–10% n.d.c.) and high radiochemical purity (>99%); 7β-[18F]FCA and 12β-[18F]FCA could not be synthesized and included further in this study. In vitro evaluation showed that 3α-FCA, 3β-FGCA, and 3β-FCDCA all had a low micromolar Ki-value for NTCP, OATP1B1, and BSEP. In vivo, 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA displayed hepatobiliary transport with varying efficiency. A slight yet significant difference in uptake and efflux rate was noticed between the 3α-[18F]FCA and 3β-[18F]FCA epimers. Conjugation of 3β-[18F]FCA with glycine had no significant effect in vivo. Compound 3β-[18F]FCDCA showed a significantly slower hepatic uptake and efflux towards gallbladder and intestines. Conclusion. A set of 18F labeled bile acids was synthesized that are substrates of the bile acid transporters in vitro and in vivo and can serve as PET-biomarkers for hepatobiliary transport of bile acids.

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