Correlation of Organic Cation/Carnitine Transporter 1 and Multidrug Resistance-Associated Protein 1 Transport Activities with Protein Expression Levels in Primary Cultured Human Tracheal, Bronchial, and Alveolar Epithelial Cells

Atsushi Sakamoto, Shinobu Suzuki, Takehisa Matsumaru, Norio Yamamura, Yasuo Uchida, Masanori Tachikawa, Tetsuya Terasaki

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Understanding how transporters contribute to the distribution of inhaled drugs in the lung is important for the discovery and development of such drugs. Protein expression levels may be useful to predict and understand drug distribution. As previously reported, organic cation/carnitine transporter 1 (OCTN1) and multidrug resistance-associated protein 1 (MRP1) have higher levels of protein expression among transporters in primary cultured human lung cells. Nevertheless, it is unclear to what extent transport activity correlates with transporter protein expression. The purpose is to evaluate whether differences in OCTN1 and MRP1 protein expression govern the respective transport activity in primary cultured human lung cells. The model substrates of 4-[4-(dimethylamino) styryl]-N-methylpyridinium iodide (ASP+) and carboxy-dichlorofluorescein (CDF) for OCTN1 and MRP1, respectively, were used in the lung cells from five donors. Significant correlation was found between the kinetic parameter Vmax for ASP+ and OCTN1 protein expression in plasma membrane of tracheal, bronchial, and alveolar cells (r2 = 0.965, 0.834, and 0.877, respectively), and between the efflux of CDF and MRP1 protein expression in plasma membrane of tracheal, bronchial, and alveolar cells (r2 = 0.800, 0.904, and 0.790, respectively). These findings suggest that OCTN1 and MRP1 protein concentrations are determinants for drug distribution in the lung.

Original languageEnglish
Pages (from-to)876-883
Number of pages8
JournalJournal of Pharmaceutical Sciences
Volume105
Issue number2
DOIs
Publication statusPublished - 2016 Feb 1

Keywords

  • ABC transporters
  • drug transport
  • individualized drug therapy
  • mass spectrometry
  • membrane transporter
  • multidrug resistance-associated proteins
  • organic cation transporters (OCT)
  • proteomics
  • pulmonary drug delivery
  • targeted drug delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

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