Hepatic bile salt flux does not modulate level and activity of the sinusoidal Na+-taurocholate cotransporter (ntcp) in rats.
OBJECTIVE
Efficient uptake at the basolateral plasma membrane of hepatocytes is required for maintenance of the enterohepatic circulation of bile salts. Uptake occurs mainly via a Na+-dependent process mediated by ntcp, a recently cloned and characterized 51 kDa glycoprotein. The aim of this study was to evaluate the role of variations in hepatic bile salt flux through the liver in the regulation of ntcp activity and expression under non-cholestatic conditions.


METHODS
We determined the kinetics of Na+-dependent taurocholate transport in isolated basolateral plasma membrane vesicles as well as hepatic ntcp protein and ntcp mRNA levels in long-term (8 days) bile-diverted rats, with a transhepatic bile salt flux of 0, and in streptozotocin-induced diabetic rats with a 2.5-fold increased bile salt flux.


RESULTS
We found no changes in the kinetics of taurocholate transport in the absence of transhepatic bile salt flux due to bile diversion. Ntcp protein and ntcp mRNA levels were also unaffected in bile-diverted rats. Likewise, no changes in taurocholate transport kinetics, ntcp protein or ntcp mRNA levels were detected in streptozotocin-diabetic rats when compared to non-diabetic controls. Thus, variation in hepatic bile salt flux from 0 to 250% of normal values had no effect on hepatic ntcp expression or taurocholate transport activity in basolateral plasma membrane vesicles in rats. In contrast, 4 days of bile duct ligation resulted in a strong decrease in ntcp mRNA and protein levels, as recently also reported by others.


CONCLUSIONS
Our data indicate that ntcp is not regulated by the transhepatic flux of bile acids under non-cholestatic conditions.
Koopen
N R
NR
Groningen Institute for Drug Studies, University Hospital Groningen, The Netherlands.
Wolters
H
H
Müller
M
M
Schippers
I J
IJ
Havinga
R
R
Roelofsen
H
H
Vonk
R J
RJ
Stieger
B
B
Meier
P J
PJ
Kuipers
F
F
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters; D013656:Taurocholic Acid / Q000378:metabolism
D001647:Bile Acids and Salts; D002352:Carrier Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; D027981:Symporters; C071908:sodium-bile acid cotransporter; D013656:Taurocholic Acid