STEREOSELECTIVE BLOOD-BRAIN-BARRIER TRANSPORT OF HISTIDINE IN RATS

The transport characteristics of L- and D-histidine through the blood- brain barrier (BBB) were studied using cultured rat brain microvascula r endothelial cells (BMEC). L-Histidine uptake was a saturable process . A decrease in incubation temperature from 37 to 0 degrees C or the a ddition of metabolic inhibitors (DNP and rotenone) reduced the uptake rate of L-histidine. Ouabain, an inhibitor of (Na+, K+)-ATPase, also r educed uptake of L-histidine. Moreover, the substitution of Na+ with c holine chloride and choline bicarbonate in the incubation buffer decre ased the initial L- and D-histidine uptake rates. These results sugges ted that L-histidine is actively uptaken by a carrier-mediated mechani sm into the BMEC, with energy supplied by Na+. However, L-histidine up take at 0 degrees C was not completely inhibited, and it was reduced i n the presence of an Naf-independent System-L substrate, BCH, suggesti ng facilitated diffusion (the Na+-independent process) by a carrier-me diated mechanism into the BMEC. L-histidine uptake in rat BMEC also ap peared to be System-N mediated since uptake was inhibited by glutamine , aspargine and L-glutamic acid gamma-monohydroxamate. System-N mediat ed transport was not pH sensitive. D-histidine transport was also stud ied in rat BMEC. D-histidine transport by rat BMEC has similar charact eristics to L-histidine. However, System-N transport did not play a ro le in D-histidine uptake. The uptake of L-histidine was also greater t han that of the D-isomer, indicating the stereoselective uptake of his tidine in rat BMEC. (C) 1998 Elsevier Science B.V. All rights reserved .