Sodium and chloride ion-dependent transport of beta-alanine across the blood-brain barrier.
The characteristics of beta-alanine transport at the blood-brain barrier were studied by using primary cultured bovine brain capillary endothelial cells. Kinetic analysis of the beta-[3H]alanine transport indicated that the transporter for beta-alanine functions with Kt of 25.3 +/- 2.5 microM and Jmax of 6.90 +/- 0.48 nmol/30 min/mg of protein in the brain capillary endothelial cells. Beta-[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 beta-[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 beta-alanine molecule. The Na+ and Cl--dependent uptake of beta-[3H]alanine was stimulated by a valinomycin-induced inside-negative K+-diffusion potential. beta-Amino acids (beta-alanine, taurine, and hypotaurine) inhibited strongly the uptake of beta-[3H]-alanine, whereas alpha- and gamma-amino acids had little or no inhibitory effect. In ATP-depleted cells, the uptake of beta-[3H]alanine was stimulated by preloading of beta-alanine or taurine but not L-leucine. These results show that beta-alanine is taken up by brain capillary endothelial cells, via the secondary active transport mechanism that is common to beta-amino acids.
Komura
J
J
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan.
Tamai
I
I
Senmaru
M
M
Terasaki
T
T
Sai
Y
Y
Tsuji
A
A
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D017920:Antiporters / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000166:cytology; D002417:Cattle; D002478:Cells, Cultured / Q000502:physiology; D002712:Chlorides / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D017136:Ion Transport / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D012964:Sodium / Q000502:physiology*; D012965:Sodium Chloride / Q000378:metabolism; D013654:Taurine / Q000378:metabolism; D013997:Time Factors; D014316:Tritium / Q000378:metabolism; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000378:metabolism*
D000596:Amino Acids; D017920:Antiporters; D002712:Chlorides; D014316:Tritium; D015091:beta-Alanine; D013654:Taurine; D012965:Sodium Chloride; D012964:Sodium