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

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Hagenbuch N, Reichel C, Stieger B, Cattori V, Fattinger KE, Landmann L, Meier PJ, Kullak-Ublick GA

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

J Hepatol. 2001 Jun;34(6):881-7.

PubMed ID

11451172 [ View in PubMed

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Abstract

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; Slc21aS) more than 2-fold on the RNA (P < 0.05) and protein (P < 0.001) levels. Expression of Oatpl (Slc21al), 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 Oatpl and Oatp4 expression is in accordance with unchanged BSP uptake. These data challenge the previously held view that PB induces hepatocellular BSP uptake systems.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Digoxin	Bile salt export pump	Protein	Humans	Unknown	Substrate	Details
Digoxin	Solute carrier organic anion transporter family member 1B1	Protein	Humans	Unknown	Substrate Inhibitor	Details
Phenobarbital	Solute carrier organic anion transporter family member 2A1	Protein	Humans	Unknown	Inducer	Details