P-glycoprotein-mediated transcellular transport of MDR-reversing agents

Tohru Saeki, Kazumitsu Ueda, Yusuke Tanigawara, Ryohei Hori, Tohru Komano

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Understanding of the interactions between P-glycoprotein and multidrug resistance (MDR) reversing agents is important in designing more effective MDR modulators. We examined transcellular transport of several MDR modulators by using a drug-sensitive epithelial cell line, LLC-PK1 and its transformant cell line, LLC-GA5-COL300, which expresses human P-glycoprotein on the apical surface. Basal-to-apical transports of azidopine and diltiazem across the LLC-GA5-COL300 monolayer were increased and apical-to-basal transports were decreased compared to those across the LLC-PK1 monolayer, indicating that P-glycoprotein transports azidopine and diltiazem. Movements of nitrendipine and staurosporine across the epithelial monolayer were not affected by P-glycoprotein. These results suggests that some MDR modulators exert their inhibitory effect not only by blocking the initial binding of anticancer drugs but throughout the course of the transport process.

Original languageEnglish
Pages (from-to)99-102
Number of pages4
JournalFEBS Letters
Volume324
Issue number1
DOIs
Publication statusPublished - 1993 Jun 7
Externally publishedYes

Fingerprint

Transcytosis
Multiple Drug Resistance
P-Glycoprotein
Modulators
Monolayers
Diltiazem
Nitrendipine
Cell Line
Staurosporine
Pharmaceutical Preparations
Epithelial Cells
Cells
azidopine

Keywords

  • LLC-PK
  • MDR modulator
  • Multidrug resistance
  • P-glycoprotein
  • Transcellular transport

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

P-glycoprotein-mediated transcellular transport of MDR-reversing agents. / Saeki, Tohru; Ueda, Kazumitsu; Tanigawara, Yusuke; Hori, Ryohei; Komano, Tohru.

In: FEBS Letters, Vol. 324, No. 1, 07.06.1993, p. 99-102.

Research output: Contribution to journalArticle

Saeki, Tohru ; Ueda, Kazumitsu ; Tanigawara, Yusuke ; Hori, Ryohei ; Komano, Tohru. / P-glycoprotein-mediated transcellular transport of MDR-reversing agents. In: FEBS Letters. 1993 ; Vol. 324, No. 1. pp. 99-102.
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