title: Involvement of a novel organic cation transporter in verapamil transport across the inner blood-retinal barrier.
abstract: OBJECTIVE
  To clarify the transport and inhibition characteristics involved in verapamil transport across the inner blood-retinal barrier (inner BRB).
  
  
  METHODS
  The transport of [(3)H]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 [(3)H]verapamil was 614 μL/(min·g retina), which is 4.7-fold greater than that of brain. The retinal uptake of [(3)H]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 [(3)H]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.
authors.affiliation: Department of Pharmaceutics Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630, Sugitani, Toyama, 930-0194, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kubo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kusagawa
authors.forename: Masanori
authors.initials: M
authors.lastname: Tachikawa
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Akanuma
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Hosoya
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000378:metabolism*; D001692:Biological Transport; D001813:Blood-Retinal Barrier / Q000378:metabolism*; D002412:Cations / Q000378:metabolism; D002460:Cell Line; D008297:Male; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D011738:Pyrilamine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000378:metabolism*; D014700:Verapamil / Q000378:metabolism*
chemical_list: D000889:Anti-Arrhythmia Agents; D002412:Cations; D027701:Organic Cation Transport Proteins; D014665:Vasodilator Agents; D014700:Verapamil; D011738:Pyrilamine