Na(+)- and Cl(-)-dependent transport of taurine at the blood-brain barrier.
The characteristics of carrier-mediated transport of taurine at the blood-brain barrier (BBB) were studied by using primary cultured bovine brain capillary endothelial cells (BCECs), in situ brain perfusion and brain capillary depletion methods in rats. The uptake of [3H]taurine by cultured cells showed that the active transporter functions on both the luminal and antiluminal membranes of BCECs. The kinetic parameters for the saturable transport of taurine were estimated to be: for the luminal uptake, the Michaelis constant, Kt, was 12.1 +/- 0.5 microM, and the maximum uptake rate, Jmax, was 4.32 +/- 0.05 nmol/30 min/mg protein; for the antiluminal uptake, Kt was 13.6 +/- 2.4 microM and Jmax was 2.81 +/- 0.22 nmol/30 min/mg protein. The luminal and antiluminal uptakes of [3H]taurine were each dependent on both Na+ Cl-. Stoichiometric analyses suggest that two Na+ and one Cl- are associated with the luminal uptake of one taurine molecule. beta-Amino acids such as beta-alanine and hypotaurine strongly inhibited the uptake of [3H]taurine, whereas alpha- and gamma-amino acids had little or no effect. Furthermore, by in situ brain perfusion and in vivo brain capillary depletion methods, the carrier-mediated transport found by in vitro experiments was confirmed to function for the translocation of the taurine molecule from the vascular space into the brain. From these results, it was concluded that a Na+ and Cl- gradient-dependent transport (uptake) system for taurine exists in both the luminal and the antiluminal membranes of BCECs.
Tamai
I
I
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Senmaru
M
M
Terasaki
T
T
Tsuji
A
A
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002196:Capillaries / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology; D013395:Sucrose / Q000378:metabolism; D013654:Taurine / Q000378:metabolism*; D013696:Temperature
D000596:Amino Acids; D002712:Chlorides; D013654:Taurine; D013395:Sucrose; D012964:Sodium