Characterization of the mechanism of zidovudine uptake by rat conditionally immortalized syncytiotrophoblast cell line TR-TBT

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

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1647-1653
Number of pages7
JournalPharmaceutical Research
Volume25
Issue number7
DOIs
Publication statusPublished - 2008 Jul

Fingerprint

Nucleoside Transport Proteins
Probenecid
Zidovudine
Trophoblasts
Nucleosides
Rats
Cells
Organic Anion Transporters
Cell Line
Deoxyuridine
Reverse Transcriptase Inhibitors
Cimetidine
Thymidine
Cyclosporine
Cations
Sodium

Keywords

  • AZT
  • Blood-placenta barrier
  • Syncytiotrophoblast
  • TR-TBT
  • Transporter

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmaceutical Science
  • Pharmacology

Cite this

Characterization of the mechanism of zidovudine uptake by rat conditionally immortalized syncytiotrophoblast cell line TR-TBT. / Sai, Y.; Nishimura, Tomohiro; Shimpo, S.; Chishu, T.; Sato, K.; Kose, N.; Terasaki, T.; Mukai, C.; Kitagaki, S.; Miyakoshi, N.; Kang, Y. S.; Nakashima, E.

In: Pharmaceutical Research, Vol. 25, No. 7, 07.2008, p. 1647-1653.

Research output: Contribution to journalArticle

Sai, Y, Nishimura, T, Shimpo, S, Chishu, T, Sato, K, Kose, N, Terasaki, T, Mukai, C, Kitagaki, S, Miyakoshi, N, Kang, YS & Nakashima, E 2008, 'Characterization of the mechanism of zidovudine uptake by rat conditionally immortalized syncytiotrophoblast cell line TR-TBT', Pharmaceutical Research, vol. 25, no. 7, pp. 1647-1653. https://doi.org/10.1007/s11095-008-9564-9
Sai, Y. ; Nishimura, Tomohiro ; Shimpo, S. ; Chishu, T. ; Sato, K. ; Kose, N. ; Terasaki, T. ; Mukai, C. ; Kitagaki, S. ; Miyakoshi, N. ; Kang, Y. S. ; Nakashima, E. / Characterization of the mechanism of zidovudine uptake by rat conditionally immortalized syncytiotrophoblast cell line TR-TBT. In: Pharmaceutical Research. 2008 ; Vol. 25, No. 7. pp. 1647-1653.
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AU - Chishu, T.

AU - Sato, K.

AU - Kose, N.

AU - Terasaki, T.

AU - Mukai, C.

AU - Kitagaki, S.

AU - Miyakoshi, N.

AU - Kang, Y. S.

AU - Nakashima, E.

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N2 - 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.

AB - 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.

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