Donepezil, tacrine and α-phenyl-n-tert-butyl nitrone (PBN) inhibit choline transport by conditionally immortalized rat brain capillary endothelial cell lines (TR-BBB)

  • Young-Sook Kang
  • Kyeong-Eun Lee
  • Na-Young Lee
  • Tetsuya Terasaki
Drug development


In the present study, we have characterized the choline transport system and examined the influence of various amine drugs on the choline transporter using a conditionally immortalized rat brain capillary endothelial cell line (TR-BBB)in vitro. The cell-to-medium (C/M) ratio of [3H]choline in TR-BBB cells increased time-dependently. The initial uptake rate of [3H]choline was concentration-dependent with a Michaelis-Menten value, Km, of 26.2 ± 2.7 μM. The [3H]choline uptake into TR-BBB was Na+-independent, but was membrane potential-dependent. The [3H]choline uptake was susceptible to inhibition by hemicholinium-3, and tetraethy-lammonium (TEA), which are organic cation transporter substrates. Also, the uptake of [3H]choline was competitively inhibited withK i values of 274 μM, 251 μM and 180 μM in the presence of donepezil hydrochloride, tacrine and α-phenyl-n-tert-butyl nitrone (PBN), respectively. These characteristics of choline transport are consistent with those of the organic cation transporter (OCT). OCT2 mRNA was expressed in TR-BBB cells, while the expression of OCT3 or choline transporter (CHT) was not detected. Accordingly, these results suggest that OCT2 is a candidate for choline transport at the BBB and may influence the BBB permeability of amine drugs.

Key words

Donepezil, tacrine PBN Choline transport Organic cation transporter Blood-brain barrier Rat brain capillary endothelial cell line 


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Copyright information

© The Pharmaceutical Society of Korea 2005

Authors and Affiliations

  • Young-Sook Kang
    • 2
  • Kyeong-Eun Lee
    • 2
  • Na-Young Lee
    • 2
  • Tetsuya Terasaki
    • 1
    • 2
  1. 1.Department of Molecular Biopharmacy and Genetics, Graduate School of Pharmaceutical SciencesTohoku UniversitySendaiJapan
  2. 2.College of PharmacySookmyung Women’s UniversitySeoulKorea

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