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 [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 tetraethylammonium (TEA), which are organic cation transporter substrates. Also, the uptake of [3H]choline was competitively inhibited with Ki 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.
Original language | English |
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Pages (from-to) | 443-450 |
Number of pages | 8 |
Journal | Archives of Pharmacal Research |
Volume | 28 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2005 Apr 30 |
Keywords
- Blood-brain barrier
- Choline transport
- Donepezil
- Organic cation transporter
- PBN
- Rat brain capillary endothelial cell line
- Tacrine
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
- Organic Chemistry