Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter.

Article Details

Citation

Hagenbuch B, Meier PJ

Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter.

J Clin Invest. 1994 Mar;93(3):1326-31.

PubMed ID
8132774 [ View in PubMed
]
Abstract

We have used a cDNA probe from a cloned rat liver Na+/taurocholate cotransporting polypeptide (Ntcp) to screen a human liver cDNA library. A 1,599-bp cDNA clone that encodes a human Na+/taurocholate cotransporting polypeptide (NTCP) was isolated. The human NTCP consists of 349 amino acids (calculated molecular mass of 38 kD) and exhibits 77% amino acid homology with the rat Ntcp. In vitro translation experiments indicate that the protein is glycosylated and has a molecular weight similar to the rat Ntcp. Injection of in vitro transcribed cRNA into Xenopus laevis oocytes resulted in the expression of Na(+)-dependent taurocholate uptake. Saturation kinetics indicated that the human NTCP has a higher affinity for taurocholate (apparent Km = 6 microM) than the previously cloned rat protein (apparent Km = 25 microM). NTCP-mediated taurocholate uptake into oocytes was inhibited by all major bile acid derivatives (100 microM), bumetanide (500 microM), and bromosulphophthalein (100 microM). Southern blot analysis of genomic DNA from a panel of human/hamster somatic cell hybrids mapped the human NTCP gene to chromosome 14.

DrugBank Data that Cites this Article

Drugs
Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
Taurocholic acidCystine/glutamate transporterProteinHumans
Unknown
Not AvailableDetails
Polypeptides
NameUniProt ID
Sodium/bile acid cotransporterQ14973Details