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

Autor: Lukas Landmann, Valentino Cattori, Karin Fattinger, Bruno Stieger, Gerd A. Kullak-Ublick, Peter J. Meier, Niels Hagenbuch, Christoph Reichel
Přispěvatelé: University of Zurich, Kullak-Ublick, G A
Rok vydání: 2001
Předmět:
Male
Digoxin
Organic anion transporter 1
Gene Expression
Organic Anion Transporters
Sodium-Independent
Sulfobromophthalein
Rats
Sprague-Dawley
0302 clinical medicine
ABCB11
ATP Binding Cassette Transporter
Subfamily B
Member 11
0303 health sciences
Symporters
biology
Multidrug resistance-associated protein 2
Multidrug Resistance-Associated Protein 2
Organic anion-transporting polypeptide
medicine.anatomical_structure
Liver
Phenobarbital
030220 oncology & carcinogenesis
Hepatocyte
Multidrug Resistance-Associated Proteins
medicine.medical_specialty
Biological Transport
Active
Organic Anion Transporters
Sodium-Dependent
610 Medicine & health
In Vitro Techniques
Bile Acids and Salts
Solute Carrier Organic Anion Transporter Family Member 1B3
03 medical and health sciences
Organic Anion Transport Protein 1
Cholestasis
Internal medicine
medicine
Animals
RNA
Messenger
030304 developmental biology
SLC10A1
Hepatology
Membrane Transport Proteins
medicine.disease
Bile Salt Export Pump
Rats
Kinetics
Endocrinology
10199 Clinic for Clinical Pharmacology and Toxicology
Hepatocytes
biology.protein
ATP-Binding Cassette Transporters
2721 Hepatology
Carrier Proteins
Zdroj: Journal of Hepatology. 34:881-887
ISSN: 0168-8278
DOI: 10.1016/s0168-8278(01)00097-6
Popis: Background/Aims : The hepatic clearance of drugs and cholephilic organic anions is stimulated by phenobarbital (PB). Our aim was to analyze the effects of PB on the expression of hepatocellular bile salt and organic anion transporters. Methods : Male Sprague–Dawley rats were treated intraperitoneally with PB (80 mg/kg/d) or saline for 5 days. Transporter expression was quantified by northern and western blot analysis and initial uptake rates of bromosulphophthalein (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 Slc21a1 ), Oatp4 ( Slc21a6 ) and the Na + -taurocholate cotransporting polypeptide (Ntcp; Slc10a1 ) was unaltered. At the canalicular pole, expression of the bile salt export pump (Bsep; ABCB11 ) and of the multidrug resistance proteins 2 (Mrp2; ABCC2 ) and 6 (Mrp6; ABCC6 ) was not significantly changed. Whereas hepatocellular BSP uptake was unaffected by PB, digoxin uptake was stimulated 4-fold. Conclusions : The induction of digoxin uptake by PB correlates with Oatp2 expression. In contrast, the lack of increase of Oatp1 and Oatp4 expression is in accordance with unchanged BSP uptake. These data challenge the previously held view that PB induces hepatocellular BSP uptake systems.
Databáze: OpenAIRE
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