Transport characteristics of mouse concentrative nucleoside transporter 1
Autor: | Sadaki Fujimoto, Kentaro Nishida, Katsuhito Nagai, Hiroto Okuda, Miho Niitani, Kazuki Nagasawa |
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Rok vydání: | 2009 |
Předmět: |
Purine
Male Pharmaceutical Science Biology Substrate Specificity Concentrative nucleoside transporter chemistry.chemical_compound Zalcitabine Mice Species Specificity Chlorocebus aethiops medicine Animals Humans Nucleoside analogue Sodium Membrane Transport Proteins Equilibrative nucleoside transporter Biological Transport Nucleosides Stereoisomerism Deoxyuridine Uridine chemistry Biochemistry COS Cells Models Animal biology.protein Nucleoside medicine.drug |
Zdroj: | International journal of pharmaceutics. 388(1-2) |
ISSN: | 1873-3476 |
Popis: | Concentrative nucleoside transporter 1 (CNT1, SLC28A1) is a key molecule for determining the pharmacokinetic/pharmacodynamic profile of a candidate compound derived from a pyrimidine nucleoside, but there is no available information on the differences in the functional profile of this ortholog between man and mouse. Here, using a clone of mouse CNT1 (mCNT1), we investigated its transport characteristics and substrate specificity for synthetic nucleoside analogues, and compared them with those of human CNT1 (hCNT1). In mCNT1-transfected Cos-7 cells, pyrimidine, but not purine, nucleosides showed sodium- and concentration-dependent uptake, and uridine uptake was competitively inhibited by uridine analogues, the rank order of the inhibitory effects being 5-bromouridine>3'-deoxyuridine>2'-deoxyuridine. cis- and trans-Inhibition studies involving synthetic nucleoside drugs revealed that gemcitabine and zidovudine greatly inhibited [(3)H]uridine uptake mediated by mCNT1 in the both cases, while cytarabine and zalcitabine showed small cis-inhibitory effect, and no trans-inhibitory effect on the uptake. These results demonstrate that the transport characteristics of mCNT1 are almost the same as those of hCNT1, suggesting that mice may be a good animal model in evaluation of pyrimidine nucleoside analogues as to their applicability in human therapy. |
Databáze: | OpenAIRE |
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