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Characterization of the Mechanism of Zidovudine Uptake by Rat Conditionally Immortalized Syncytiotrophoblast Cell Line TR-TBT

Sai, Y. ; Nishimura, T. ; Shimpo, S. ; Chishu, T. ; Sato, K. ; Kose, N. ; Terasaki, T. ; Mukai, C. ; Kitagaki, S. ; Miyakoshi, N. ; Kang, Y.-S. ; Nakashima, E.

Pharmaceutical research, 2008-07, Vol.25 (7), p.1647-1653 [Periódico revisado por pares]

Boston: Springer US

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Título:
Characterization of the Mechanism of Zidovudine Uptake by Rat Conditionally Immortalized Syncytiotrophoblast Cell Line TR-TBT
Autor: Sai, Y. ; Nishimura, T. ; Shimpo, S. ; Chishu, T. ; Sato, K. ; Kose, N. ; Terasaki, T. ; Mukai, C. ; Kitagaki, S. ; Miyakoshi, N. ; Kang, Y.-S. ; Nakashima, E.
Assuntos: Algorithms ; Animals ; Anti-HIV Agents - metabolism ; Biochemistry ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Biomedicine ; Cell Line ; Cell Membrane - metabolism ; Data Interpretation, Statistical ; Drug Interactions ; General pharmacology ; Giant Cells - cytology ; Giant Cells - metabolism ; HIV ; Human immunodeficiency virus ; Medical Law ; Medical sciences ; Nucleoside Transport Proteins - antagonists & inhibitors ; Nucleoside Transport Proteins - metabolism ; Organic Anion Transporters - antagonists & inhibitors ; Organic Anion Transporters - metabolism ; Organic Cation Transport Proteins - antagonists & inhibitors ; Organic Cation Transport Proteins - metabolism ; Pharmaceutical sciences ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Pharmacology/Toxicology ; Pharmacy ; Placenta ; Rats ; Research Paper ; Trophoblasts - metabolism ; Zidovudine - metabolism
É parte de: Pharmaceutical research, 2008-07, Vol.25 (7), p.1647-1653
Descrição: Purpose To characterize the uptake mechanism of zidovudine (AZT), a nucleoside reverse transcriptase inhibitor, in syncytiotrophoblast cells using the TR-TBT 18d-1 cell line previously established by our group. Materials and Methods The effects of several transporter inhibitors on the initial and steady-state apical uptake of AZT by TR-TBT 18d-1 were characterized, in order to identify the transporter(s) involved. Results Initial uptake of AZT was sodium-independent and saturable; the K m value was about 16 μM. Nitrobenzylthioinosine (NBMPR), probenecid and cimetidine each had little effect on the saturable AZT uptake, indicating that well characterized transporters, such as organic anion transporters (OATs and OATPs), organic cation transporters (OCTs) and equilibrative nucleoside transporters (ENTs), are not involved. However, thymidine and 2′-deoxyuridine strongly inhibited AZT uptake. These results suggest that an unidentified nucleoside uptake transporter is responsible for the uptake of AZT. Cyclosporin A, Ko143 and probenecid had little effect on AZT accumulation by TR-TBT 18d-1 cells, suggesting that transporter-mediated efflux of AZT is not substantial. Conclusion Our results indicate that saturable AZT uptake into TR-TBT 18d-1 is mediated by a so-far-unidentified transporter.
Editor: Boston: Springer US
Idioma: Inglês

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Characterization of the Mechanism of Zidovudine Uptake by Rat Conditionally Immortalized Syncytiotrophoblast Cell Line TR-TBT

Sai, Y. ; Nishimura, T. ; Shimpo, S. ; Chishu, T. ; Sato, K. ; Kose, N. ; Terasaki, T. ; Mukai, C. ; Kitagaki, S. ; Miyakoshi, N. ; Kang, Y.-S. ; Nakashima, E.

Boston: Springer US

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