Potential Cholestatic Activity of Various Therapeutic Agents Assessed by Bile Canalicular Membrane Vesicles Isolated from Rats and Humans

2003 ◽  
Vol 18 (1) ◽  
pp. 16-22 ◽  
Author(s):  
Masato Horikawa ◽  
Yukio Kato ◽  
Charles A. Tyson ◽  
Yuichi Sugiyama
Keyword(s):  
Membrane Vesicles ◽  
Therapeutic Agents ◽  
Canalicular Membrane ◽  
Bile Canalicular Membrane

Adenosine transport in rat liver plasma membrane vesicles

1991 ◽  
Vol 261 (5) ◽  
pp. G716-G722 ◽  
Author(s):  
R. H. Moseley ◽  
S. Jarose ◽  
P. Permoad
Keyword(s):  
Plasma Membrane ◽  
Transport Process ◽  
Membrane Vesicles ◽  
Nucleoside Transport ◽  
Plasma Membrane Vesicles ◽  
Canalicular Membrane ◽  
Liver Plasma Membrane ◽  
Adenosine Uptake ◽  
Bile Canalicular Membrane ◽  
Adenosine Transport

Liver plasma membrane ecto-ATPase activity is largely restricted to the bile canalicular membrane. To determine whether a transport process is also selectively present on this membrane surface to reclaim adenosine derived from the intracanalicular degradation of ATP, the characteristics of hepatic nucleoside transport were examined in canalicular (cLPM) and basolateral (blLPM) rat liver plasma membrane vesicles. In the presence of the adenosine deaminase inhibitor, deoxycoformycin, an inwardly directed Na+ gradient markedly stimulated [3H]adenosine uptake in cLPM vesicles. Canalicular Na(+)-dependent [3H]adenosine uptake was enhanced by an intravesicular-negative membrane potential and inhibited by dissipation of the Na+ gradient with gramicidin D. Both purine and pyrimidine nucleosides inhibited canalicular adenosine transport. 6-[(4-Nitrobenzyl)thio]-9-beta-D-ribofuranosylpurine, an inhibitor of nucleoside transport in erythrocytes and nonepithelial cells, had no effect on canalicular adenosine transport. Canalicular Na(+)-dependent [3H]adenosine uptake exhibited saturability with a Michaelis-Menten constant of 8.3 microM and a maximum transport rate of 7.6 pmol.5 s-1.mg protein-1. In contrast, [3H]adenosine uptake in blLPM vesicles was not stimulated by an inwardly directed Na+ gradient. These findings demonstrate asymmetric distribution of hepatic Na(+)-dependent nucleoside transport. Reclamation of intracanalicular adenosine resulting from ecto-ATPase activity may explain the presence of this transport process selectively on the bile canalicular membrane.

Regulation and translocation of ATP-dependent apical membrane proteins in rat liver

1997 ◽  
Vol 272 (5) ◽  
pp. G1041-G1049 ◽  
Author(s):  
Z. C. Gatmaitan ◽  
A. T. Nies ◽  
I. M. Arias
Keyword(s):  
Leucine Aminopeptidase ◽  
Specific Activity ◽  
Membrane Vesicles ◽  
Transport Proteins ◽  
Transport Processes ◽  
Western Blots ◽  
Canalicular Membrane ◽  
Transport Studies ◽  
Bile Canalicular Membrane ◽  
Dependent Transport

The bile canalicular membrane contains four specific ATP-dependent transport processes that are involved in secretion of bile acids, non-bile acid organic anions (mrp1), phospholipids (mdr2), and organic cations (mdr3). The aim of this study was to determine how the canalicular presence of these transport proteins is regulated. Canalicular membrane vesicles (CMV) were prepared from livers of rats treated with taurocholate (TC) and/or dibutyryl-adenosine 3',5'-cycle monophosphate (DBcAMP) with and without pretreatment with colchicine. Transport studies were performed with radiolabeled substrates. Changes in the relative amounts of transport proteins were determined by Western blots. Compared with controls, the specific activity of each of the transport processes was enhanced 1.5- and 3-fold with TC and DBcAMP treatments, respectively. Western blots revealed the same increases with mdr2 and mdr3. Pretreatment of rats with colchicine prevented these responses fully with TC treatment, whereas only partial prevention was obtained with DBcAMP treatment. Besides the ATP-dependent transporters, the relative specific activities of the canalicular membrane ectoenzyme markers, leucine aminopeptidase and gamma-glutamyltranspeptidase, were also affected the same way. These results suggest that TC and DBcAMP increase the specific activity of the canalicular ATP-dependent transport proteins and some canalicular membrane ectoenzymes by stimulating an increase in the relative amounts of these proteins in the membrane.

scholarly journals mdr2 encodes P-glycoprotein expressed in the bile canalicular membrane as determined by isoform-specific antibodies.

1992 ◽  
Vol 267 (25) ◽  
pp. 18093-18099
Author(s):  
E Buschman ◽  
R.J. Arceci ◽  
J.M. Croop ◽  
M Che ◽  
I.M. Arias ◽  
...  
Keyword(s):  
Canalicular Membrane ◽  
Specific Antibodies ◽  
P Glycoprotein ◽  
Bile Canalicular Membrane

Hepatic bile flow

1984 ◽  
Vol 64 (4) ◽  
pp. 1055-1102 ◽  
Author(s):  
R. C. Strange
Keyword(s):  
Bile Salt ◽  
Bile Salts ◽  
Basolateral Membrane ◽  
Membrane Vesicles ◽  
Critical Micellar Concentration ◽  
Canalicular Membrane ◽  
Receptor Proteins ◽  
Subcellular Organelles ◽  
Golgi Bodies ◽  
Initial Event

The hepatocyte is a polar cell that can remove a variety of molecules from blood and excrete them into bile. This review is primarily concerned with the mechanism of transport of the principal anions--the bile salts--across the sinusoidal membrane, their passage through the cell, and excretion across the canalicular membrane. Clearly much of this process is poorly understood, but the study of the membrane stages should be facilitated by the ability to prepare purified sinusoidal and canalicular membrane vesicles. For example, the relative importance of albumin-binding sites as well as the putative bile salt receptor proteins can be better assessed. It seems likely that although the interaction of bile salts with receptor proteins is important, it is an initial event that puts the bile salt in the correct place for uptake to occur. The driving force for uptake is the Na+ gradient created across the basolateral membrane by the activity of the Na+-K+-ATPase. Within the cell, various modes of transport have been suggested. Several authors emphasize the importance of protein binding of bile salts, either because of their presumed ability to maintain the concentration of these anions in the hepatocyte below their critical micellar concentration or because of their putative role in transport. It is important to understand these aspects of the role of cytosolic proteins for several reasons. Knowledge of the true concentration of free bile salt within the cell should allow estimation of whether the electrochemical gradient is sufficient for bile salts to accumulate in bile without the need for active transport of molecules from the cell into the canaliculus. The compartmental model described by Strange et al. (153) offers one theoretical way of determining the concentration of free bile salt, although the problems inherent in studying amphipath binding to the membranes of subcellular organelles (31) require that the model be reevaluated by the hygroscopic-desorption method. The second role suggested for the cytosolic bile salt-binding proteins is as transport proteins. As discussed in section VI, I think it is unlikely that the proteins identified so far act in this way, and it is more likely that movement occurs by diffusion in free solution. It is also important to determine the possible involvement of subcellular organelles such as Golgi bodies. Little is known of their role in the transport of bile salts or indeed where bile salt micelles are formed.(ABSTRACT TRUNCATED AT 400 WORDS)

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