H Murakami1, N Sawada, N Koyabu, H Ohtani, Y Sawada. 1. Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Abstract
PURPOSE: We examined the functional properties of choline transport across the blood-brain barrier (BBB) in mice. We compared the kinetic parameters and transport properties with those found in our in vitro uptake experiments using mouse brain capillary endothelial cells (MBEC4). METHODS: The permeability coefficient-surface area product (PS) values of [3H]choline at the BBB were estimated by means of an in situ brain perfusion technique in mice. RESULTS: [3H]Choline uptake was well described by a two-component model: a saturable component and a nonsaturable linear component. The [3H]choline uptake was independent of pH and Na+, but was significantly decreased by the replacement of Na+ with K+. Various basic drugs, including substrates and inhibitors of the organic cation transporter, significantly inhibited the [3H]choline uptake. These in situ (in vivo) results corresponded well to the in vitro results and suggest that the choline transporter at the BBB is a member of the organic cation transporter (OCT) family. CONCLUSION: The choline transport mechanism at the BBB is retained in MBEC4.
PURPOSE: We examined the functional properties of choline transport across the blood-brain barrier (BBB) in mice. We compared the kinetic parameters and transport properties with those found in our in vitro uptake experiments using mouse brain capillary endothelial cells (MBEC4). METHODS: The permeability coefficient-surface area product (PS) values of [3H]choline at the BBB were estimated by means of an in situ brain perfusion technique in mice. RESULTS: [3H]Choline uptake was well described by a two-component model: a saturable component and a nonsaturable linear component. The [3H]choline uptake was independent of pH and Na+, but was significantly decreased by the replacement of Na+ with K+. Various basic drugs, including substrates and inhibitors of the organic cation transporter, significantly inhibited the [3H]choline uptake. These in situ (in vivo) results corresponded well to the in vitro results and suggest that the choline transporter at the BBB is a member of the organic cation transporter (OCT) family. CONCLUSION: The choline transport mechanism at the BBB is retained in MBEC4.
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