Lysosomal trapping is present in retinal capillary endothelial cells: Insight into its influence on cationic drug transport at the inner blood-retinal barrier

Yoshiyuki Kubo, Narumi Seko, Takuya Usui, Shin Ichi Akanuma, Ken Ichi Hosoya

研究成果: Article査読

9 被引用数 (Scopus)

抄録

Lysosomal trapping was investigated in the retinal capillary endothelial cells that are responsible for the inner blood-retinal barrier (BRB) using LysoTracker® Red (LTR). Using confocal microscopy on TR-iBRB2 cells, an in vitro model of the inner BRB, the presence of lysosomal trapping in retinal capillary endothelial cells was suggested since TR-iBRB2 cells exhibited punctuate intracellular localization of LTR that was attenuated by NH4Cl treatment. The study confirmed that LTR uptake by retinal capillary endothelial cells took place in a time- and temperature-dependent manner, and exhibited the 1.58-fold greater uptake at pH 8.4 than that at pH 7.4 while there was no change in uptake between pH 6.4 and pH 7.4, suggesting that passive diffusion is not enough to explain LTR uptake. The inhibition study showed the possible influence of lysosomal trapping on cationic drug transport by retinal capillary endothelial cells since LTR uptake was significantly inhibited by cationic amphiphilic drugs. Inhibition profiling and the estimation of IC50 suggested the influence of lysosomal trapping on propranolol and low-affinity pyrilamine transport while lysosomal trapping had only a partial effect on verapamil, clonidine, nicotine and high-affinity pyrilamine transport in retinal capillary endothelial cells.

本文言語English
ページ(範囲)1319-1324
ページ数6
ジャーナルBiological and Pharmaceutical Bulletin
39
8
DOI
出版ステータスPublished - 2016
外部発表はい

ASJC Scopus subject areas

  • 薬理学
  • 薬科学

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