Characterization of 6-Mercaptopurine Transport by the SLC43A3-Encoded Nucleobase Transporter.


Journal

Molecular pharmacology
ISSN: 1521-0111
Titre abrégé: Mol Pharmacol
Pays: United States
ID NLM: 0035623

Informations de publication

Date de publication:
06 2019
Historique:
received: 11 09 2018
accepted: 14 03 2019
pubmed: 27 3 2019
medline: 18 12 2019
entrez: 27 3 2019
Statut: ppublish

Résumé

6-Mercaptopurine (6-MP) is a nucleobase analog used in the treatment of acute lymphoblastic leukemia and inflammatory bowel disorders. However, the mechanisms underlying its transport into target cells have remained elusive. The protein encoded by SLC43A3_1 [equilibrative nucleobase transporter 1 (ENBT1)] has recently been shown to transport endogenous nucleobases. A splice variant (SLC43A3_2), encoding a protein with 13 additional amino acids in the first extracellular loop, is also expressed but its function is unknown. We hypothesized that 6-MP is a substrate for both variants of ENBT1. Human embryonic kidney 293 (HEK293) cells (lacking endogenous ENBT1 activity) were transfected with each of the coding region variants of SLC43A3. ENBT1 function was assessed via the rate of flux of [

Identifiants

pubmed: 30910793
pii: mol.118.114389
doi: 10.1124/mol.118.114389
doi:

Substances chimiques

ABCC4 protein, human 0
Amino Acid Transport Systems 0
Multidrug Resistance-Associated Proteins 0
SLC43A3 protein, human 0
Mercaptopurine E7WED276I5

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

584-596

Informations de copyright

Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.

Auteurs

Nicholas M Ruel (NM)

Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada.

Khanh H Nguyen (KH)

Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada.

Gonzalo Vilas (G)

Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada.

James R Hammond (JR)

Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada james.hammond@ualberta.ca.

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Classifications MeSH