Involvement of a novel organic cation transporter in verapamil transport across the inner blood-retinal barrier

Yoshiyuki Kubo, Yusuke Kusagawa, Masanori Tachikawa, Shin Ichi Akanuma, Ken Ichi Hosoya

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Purpose: To clarify the transport and inhibition characteristics involved in verapamil transport across the inner blood-retinal barrier (inner BRB). Methods: The transport of [3H]verapamil across the inner BRB was investigated using retinal uptake index and integration plot analyses in rats. The detailed transport characteristics were studied using TR-iBRB2 cells, a conditionally immortalized rat retinal capillary endothelial cell line that is an in vitro model of the inner BRB. Results: The apparent influx permeability clearance of [3H]verapamil was 614 μL/(min·g retina), which is 4.7-fold greater than that of brain. The retinal uptake of [ 3H]verapamil was slightly increased by 3 mM verapamil and 10 mM qunidine and inhibited by 40 mM pyrilamine, supporting the carrier-mediated efflux and influx transport of verapamil across the inner BRB. TR-iBRB2 cells exhibited a concentration-dependent uptake of [3H]verapamil with a K m of 61.9 μM, and the uptake was inhibited by several cations, such as pyrilamine, exhibiting a different profile from the identified transporters. These transport properties suggest that verapamil transport at the inner BRB takes place via a novel organic cation transporter. Conclusions: Our findings suggest that a novel organic cation transporter is involved in verapamil transport from the blood to the retina across the inner BRB.

Original languageEnglish
Pages (from-to)847-856
Number of pages10
JournalPharmaceutical research
Volume30
Issue number3
DOIs
Publication statusPublished - 2013 Mar

Keywords

  • P-glycoprotein
  • inner blood-retinal barrier
  • lipophilic basic drug
  • organic cation transporter

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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