scholarly journals Organic anion transport across the contraluminal membrane—Dependence on sodium

1989 ◽  
Vol 36 (3) ◽  
pp. 370-377 ◽  
Author(s):  
Gerhard Burckhardt ◽  
Karl J. Ullrich
Keyword(s):  
Organic Anion ◽  
Anion Transport ◽  
Organic Anion Transport ◽  
Contraluminal Membrane

scholarly journals Characteristics of bile salt uptake into skate hepatocytes

1994 ◽  
Vol 299 (3) ◽  
pp. 665-670 ◽  
Author(s):  
G Fricker ◽  
V Dubost ◽  
K Finsterwald ◽  
J L Boyer
Keyword(s):  
Substrate Specificity ◽  
Bile Salt ◽  
Transport System ◽  
Bile Salts ◽  
Organic Anion ◽  
Anion Transport ◽  
Organic Anion Transport ◽  
Salt Uptake ◽  
Anion Transport System ◽  
Alpha 7

The substrate specificity for the transporter that mediates the hepatic uptake of organic anions in freshly isolated hepatocytes of the elasmobranch little skate (Raja erinacea) was determined for bile salts and bile alcohols. The Na(+)-independent transport system exhibits a substrate specificity, which is different from the specificity of Na(+)-dependent bile salt transport in mammals. Unconjugated and conjugated di- and tri-hydroxylated bile salts inhibit uptake of cholyltaurine and cholate competitively. Inhibition is significantly greater with unconjugated as opposed to glycine- or taurine-conjugated bile salts. However, the number of hydroxyl groups in the steroid moiety of the bile salts has only minor influences on the inhibition by the unconjugated bile salts. Since the transport system seems to represent an archaic organic-anion transport system, other anions, such as dicarboxylates, amino acids and sulphate, were also tested, but had no inhibitory effect on bile salt uptake. To clarify whether bile alcohols, the physiological solutes in skate bile, share this transport system, cholyltaurine transport was studied after addition of 5 beta-cholestane-3 beta,5 alpha,6 beta-triol, 5 alpha-cholestan-3 beta-ol and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol. These bile alcohols inhibit cholyltaurine uptake non-competitively. In contrast, uptake of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol, which is Na(+)-independent, is not inhibited by cholyltaurine. The findings further characterize a Na(+)-independent organic-anion transport system in skate liver cells, which is not shared by bile alcohols and has preference for unconjugated lipophilic bile salts.

scholarly journals Hepatocanalicular organic-anion transport is regulated by protein kinase C

1991 ◽  
Vol 278 (3) ◽  
pp. 637-641 ◽  
Author(s):  
H Roelofsen ◽  
R Ottenhoff ◽  
R P J Oude Elferink ◽  
P L M Jansen
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Organic Anion ◽  
Phosphodiesterase Inhibitor ◽  
Second Messenger ◽  
Anion Transport ◽  
Organic Anion Transport ◽  
Kinase C ◽  
Transport Assay ◽  
Messenger System

In order to investigate the regulation of canalicular organic-anion transport, we used a hepatocyte transport assay in which canalicular secretion of a model organic anion, dinitrophenyl-glutathione (GS-DNP), was measured in the presence of stimulators and inhibitors of the Ca2+/protein kinase C (PKC) second-messenger system and of the cyclic AMP (cAMP) second-messenger system. Vasopressin (24 nM) and the phorbol ester phorbol 12-myristate 13-acetate (1 microgram/ml), both stimulators of PKC, stimulated GS-DNP efflux by 65 +/- 36% and 55 +/- 28% respectively, whereas staurosporine (10 microM), an inhibitor of PKC, inhibited efflux by 53 +/- 13%. Glucagon and forskolin, both stimulators of the cAMP second-messenger system, as well as the cAMP analogue dibutyryl cAMP and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, did not significantly influence the GS-DNP efflux. It can be concluded that canalicular organic-anion transport in hepatocytes is either directly or indirectly regulated by PKC.

ATP-dependent transport of beta-estradiol 17-(beta-D-glucuronide) in rat canalicular membrane vesicles

1996 ◽  
Vol 271 (5) ◽  
pp. G791-G798
Author(s):  
M. Vore ◽  
T. Hoffman ◽  
M. Gosland
Keyword(s):  
Bile Acid ◽  
Transport System ◽  
Organic Anion ◽  
Membrane Vesicles ◽  
Anion Transport ◽  
Organic Anion Transport ◽  
Canalicular Membrane ◽  
P Glycoprotein ◽  
Anion Transport System ◽  
Dependent Transport

The ATP-dependent transport of beta-estradiol 17-(beta-D-glucuronide) (E217G), a cholestatic metabolite of estradiol, was investigated in rat liver canalicular membrane vesicles. ATP-dependent transport was dependent on time and temperature and occurred into an osmotically sensitive space; kinetic analysis indicated a saturable transport system (Michaelis-Menten constant value, 75 microM; maximum transport rate, 598 pmol.min-1.mg protein-1). The steroid conjugates estradiol glucuronide, estriol 3-glucuronide, estriol 16 alpha-glucuronide, testosterone glucuronide, and the three-sulfate conjugate of 17G were effective inhibitors of transport. Bromosulfophthalein, S-(2,4-dinitrophenyl)glutathione, and glutathione disulfide, all substrates of the canalicular ATP-dependent non-bile acid organic anion transport system, were also effective inhibitors, whereas taurocholate had no effect on transport. Conversely, E217G inhibited the ATP-dependent transport of S-(2,4-dinitrophenyl)glutathione. Daunorubicin, vinblastine, etoposide, cyclosporin, and PSC-833, substrates/modulators of P-glycoprotein, were also potent inhibitors of E217G transport, and E217G competitively inhibited the ATP-dependent transport of daunorubicin. C219, a monoclonal antibody against P-glycoprotein, inhibited ATP-dependent transport of E217G and daunorubicin but not of taurocholate or S-(2,4-dinitrophenyl)glutathione. These data indicate that E217G is substrate of both the non-bile acid organic anion transport system and P-glycoprotein but not of the ATP-dependent bile acid transport system in canalicular membranes.

Sign in / Sign up

Export Citation Format

Share Document