Uptake of L-threo-dihydroxyphenylserine into human brain synaptosomes.
Out of four diastereoisomers of 3,4-dihydroxyphenylserine (DOPS), L-threo- and L-erythro-isomer were found to be taken up into human brain synaptosomes. The uptake of L-threo-DOPS was dependent on the temperature and sensitive to the metabolic inhibitors. The L-threo-DOPS uptake proved to be saturable and carrier-mediated transport with two different kinetic characteristics; a high-affinity and low-capacity and a low-affinity and high-capacity system. The apparent Km values of these two systems were obtained to be 28.6 microM and 2.47 mM, respectively. The high-affinity transport was inhibited by glycine, L-tyrosine, L-proline, L-serine, L-Dopa, L-tryptophan, and L-phenylalanine. The inhibition by L-tyrosine was competitive in regard to L-threo-DOPS. The L-threo-DOPS uptake was inhibited by 2,4-dinitrophenol, sodium cyanide and other uncouplers of oxidative phosphorylation and by ouabain, an inhibitor of Na+, K+-ATPase, indicating that the uptake is coupled to ATP hydrolysis. On the other hand, L-threo-DOPS uptake by the low-affinity system was not inhibited by metabolic inhibitors, indicating that it may be facilitated diffusion common to high concentrations of L-amino acids.
D000596:Amino Acids / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D015103:Droxidopa / Q000493:pharmacokinetics*; D006801:Humans; D007700:Kinetics; D012694:Serine / Q000031:analogs & derivatives*; D013574:Synaptosomes / Q000378:metabolism*
D000596:Amino Acids; D012694:Serine; D015103:Droxidopa