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The Pharmaceutical Society of Korea (대한약학회)
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Donepezil, Tacrine and $\alpha-Phenyl-n-tert-Butyl Nitrone$ (PBN) Inhibit Choline Transport by Conditionally Immortalized Rat Brain Capillary Endothelial Cell Lines (TR-BBB)

  • Kang Young-Sook (College of Pharmacy, Sookmyung Women's University) ;
  • Lee Kyeong-Eun (College of Pharmacy, Sookmyung Women's University) ;
  • Lee Na-Young (College of Pharmacy, Sookmyung Women's University) ;
  • Terasaki Tetsuya (Department of Molecular Biopharmacy and Genetics, Graduate School of Pharmaceutical Sciences, Tohoku University)
  • Published : 2005.04.01
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Abstract

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 $[^3{H}]choline$ in TR-BBB cells increased time-dependently. The initial uptake rate of $[^3{H}]choline$ was concentration-dependent with a Michaelis-Menten value, $K_{m}$, of $26.2\pm2.7{\mu}M$. The $[^3{H}]choline$ uptake into TR-BBB was $Na^{+}-independent$, but was membrane potential-dependent. The $[^3{H}]choline$ uptake was susceptible to inhibition by hemicholinium-3, and tetraethy-lammonium (TEA), which are organic cation transporter substrates. Also, the uptake of $[^3{H}]choline$ was competitively inhibited with $K_{i}$ values of $274 {\mu}M, 251 {\mu}M and 180 {\mu}M$ in the presence of donepezil hydrochloride, tacrine and $\alpha-phenyl-n-tert-butyl nitrone$ (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.

Keywords

References

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