Transport of antiviral 3'-deoxy-nucleoside drugs by recombinant human and rat equilibrative, nitrobenzylthioinosine (NBMPR)-insensitive (ENT2) nucleoside transporter proteins produced in Xenopus oocytes.

Article Details

Citation
Copy to clipboard

Yao SY, Ng AM, Sundaram M, Cass CE, Baldwin SA, Young JD

Transport of antiviral 3'-deoxy-nucleoside drugs by recombinant human and rat equilibrative, nitrobenzylthioinosine (NBMPR)-insensitive (ENT2) nucleoside transporter proteins produced in Xenopus oocytes.

Mol Membr Biol. 2001 Apr-Jun;18(2):161-7.

PubMed ID
11463208 [ View in PubMed
]
Abstract

In the present study, one has determined the relative role of plasma membrane equilibrative (Na+-independent) ENT nucleoside transport proteins (particularly ENT2) in the uptake of antiviral nucleoside analogues for comparison with the previously reported drug transport properties of concentrative (Na+-dependent) CNT nucleoside transport proteins. The human and rat nucleoside transport proteins hENT1, rENT1, hENT2 and rENT2 were produced in Xenopus oocytes and investigated for their ability to transport three 3'-deoxy-nucleoside analogues, ddC (2'3'-dideoxycytidine), AZT (3'-azido-3'-deoxythymidine) and ddI (2'3'-dideoxyinosine), used in human immunodeficiency virus (HIV) therapy. The results show, for the first time, that the ENT2 transporter isoform represents a mechanism for cellular uptake of these clinically important nucleoside drugs. Recombinant h/rENT2 transported ddC, ddI and AZT, whilst h/rENT1 transported only ddC and ddI. Relative to uridine, h/rENT2 mediated substantially larger fluxes of ddC and ddI than h/rENT1. Transplanting the amino-terminal half of rENT2 into rENT1 rendered rENT1 transport-positive for AZT and enhanced the uptake of both ddC and ddI, identifying this region as a major site of 3'-deoxy-nucleoside drug interaction.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
DidanosineEquilibrative nucleoside transporter 1ProteinHumans
Unknown
Not AvailableDetails
DidanosineEquilibrative nucleoside transporter 2ProteinHumans
Unknown
Not AvailableDetails
ZalcitabineEquilibrative nucleoside transporter 1ProteinHumans
Unknown
Not AvailableDetails
ZalcitabineEquilibrative nucleoside transporter 2ProteinHumans
Unknown
Not AvailableDetails
ZidovudineEquilibrative nucleoside transporter 2ProteinHumans
Unknown
Not AvailableDetails