Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity.

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Kim RB, Leake B, Cvetkovic M, Roden MM, Nadeau J, Walubo A, Wilkinson GR

Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity.

J Pharmacol Exp Ther. 1999 Dec;291(3):1204-9.

PubMed ID

10565843 [ View in PubMed

]

Abstract

Adequate bile flow, maintained in part by the efficient enterohepatic recirculation of bile acids, is critical for normal liver function. One important component of this process is the uptake of bile acids from the portal circulation into hepatocytes by the bile acid uptake transporter sodium taurocholate cotransporting polypeptide (NTCP). Thus, the expression and functional activity of this transporter may affect the rate of bile acid removal from the portal circulation. Accordingly, we assessed NTCP mRNA expression from human livers using a sensitive RNase protection assay. In addition, the ability of various bile acids and drugs to inhibit NTCP activity was determined using a recombinant vaccinia expression system. A 40-fold interindividual variability was found in NTCP mRNA levels determined in eight liver samples of disease-free donors. Expressed NTCP exhibited high-affinity, sodium-dependent uptake of taurocholate, and as expected, this was markedly inhibited by bile acids and organic anions. A number of drugs, including peptidomimetic renin inhibitors, propranolol, cyclosporin, and progesterone, were found to be potent inhibitors, whereas antiarrhythmic agents, including bupivicaine, lidocaine, and quinidine, were found to enhance NTCP activity. Accordingly, these results indicate that large interindividual variability exists in NTCP mRNA level and that a number of drugs currently in clinical use have the potential to interact with and alter NTCP activity, thereby affecting hepatic bile acid uptake.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Progesterone	Sodium/bile acid cotransporter	Protein	Humans	Unknown	Inhibitor	Details

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Cyclosporine	Sodium/bile acid cotransporter	IC 50 (nM)	1000	N/A	N/A	Details
Ursodeoxycholic acid	Sodium/bile acid cotransporter	IC 50 (nM)	3600	N/A	N/A	Details