Effect of phenobarbital on the expression of bile salt and organic anion transporters of rat liver

Citation
N. Hagenbuch et al., Effect of phenobarbital on the expression of bile salt and organic anion transporters of rat liver, J HEPATOL, 34(6), 2001, pp. 881-887
Citations number
58
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenerology and Hepatology","da verificare
Journal title
JOURNAL OF HEPATOLOGY
ISSN journal
0168-8278 → ACNP
Volume
34
Issue
6
Year of publication
2001
Pages
881 - 887
Database
ISI
SICI code
0168-8278(200106)34:6<881:EOPOTE>2.0.ZU;2-I
Abstract
Background/Aims: The hepatic clearance of drugs and cholephilic organic ani ons is stimulated by phenobarbital (PB), Our aim was to analyze the effects of PB on the expression of hepatocellular bile salt and organic anion tran sporters. Methods: Male Sprague-Dawley rats were treated intraperitoneally with PB (8 0 mg/kg/d) or saline for 5 days. Transporter expression was quantified by n orthern and western blot analysis and initial uptake rates of bromosulphoph thalein (BSP) and digoxin were measured in isolated hepatocytes. Results: Compared to control rats, PB treatment increased expression of the organic anion transporting polypeptide 2 (Oatp2; Slc21a5) more than 2-fold on the RNA (P < 0.05) and protein (P < 0.001) levels. Expression of Oatp1 (Slc21a1), Oatp4 (Slc21a6) and the Na+-taurocholate cotransporting polypept ide (Ntcp; Slc10a1) was unaltered, At the canalicular pole, expression of t he bile salt export pump (Bsep; ABCB11) and of the multidrug resistance pro teins 2 (Mrp2; ABCC2) and 6 (Mrp6; ABCC6) was not significantly changed. Wh ereas hepatocellular BSP uptake was unaffected by PB, digoxin uptake was st imulated 4-fold. Conclusions: The induction of digoxin uptake by PB correlates with Oatp2 ex pression, In contrast, the lack of increase of Oatpl and Oatp4 expression i s in accordance with unchanged BSP uptake. These data challenge the previou sly held view that PB induces hepatocellular BSP uptake systems. (C) 2001 E uropean Association for the Study of the Liver. Published by Elsevier Scien ce B,V, All rights reserved.