Sodium and Chloride Ion-Dependent Transport of β-Alanine Across the Blood-Brain Barrier |
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Authors: | Junko Komura Ikumi Tamai Mizuho Senmaru Tetsuya Terasaki Yoshimichi Sai Akira Tsuji |
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Affiliation: | Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan |
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Abstract: | Abstract: The characteristics of β-alanine transport at the blood-brain barrier were studied by using primary cultured bovine brain capillary endothelial cells. Kinetic analysis of the β-3H]alanine transport indicated that the transporter for β-alanine functions with Kt of 25.3 ± 2.5 µ M and J max of 6.90 ± 0.48 nmol/30 min/mg of protein in the brain capillary endothelial cells. β-3H]Alanine uptake is mediated by an active transporter, because metabolic inhibitors (2,4-dinitrophenol and NaN3) and low temperature reduced the uptake significantly. Furthermore, the uptake of β-3H]alanine required Na+ and Cl? in the external medium. Stoichiometric analysis of the transport demonstrated that two sodium ions and one chloride ion are associated with one β-alanine molecule. The Na+ and Cl?-dependent uptake of β-3H]alanine was stimulated by a valinomycin-induced inside-negative K+-diffusion potential. β-Amino acids (β-alanine, taurine, and hypotaurine) inhibited strongly the uptake of β-3H]alanine, whereas α- and γ-amino acids had little or no inhibitory effect. In ATP-depleted cells, the uptake of β-3H]alanine was stimulated by preloading of β-alanine or taurine but not l -leucine. These results show that β-alanine is taken up by brain capillary endothelial cells, via the secondary active transport mechanism that is common to β-amino acids. |
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Keywords: | β-Amino acid β-Alanine Brain capillary endothelial cell Carrier-mediated uptake Brain active transporter Taurine |
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