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 microvascular endothelial cells (BMEC). l-Histidine uptake was a saturable process. A decrease in incubation temperature from 37 to 0 degreesC or the addition of metabolic inhibitors (DNP and rotenone) reduced the uptake rate of l-histidine. Ouabain, an inhibitor of (Na+, K+)-ATPase, also reduced uptake of l-histidine. Moreover, the substitution of Na+ with choline chloride and choline bicarbonate in the incubation buffer decreased the initial l- and d-histidine uptake rates. These results suggested that l-histidine is actively uptaken by a carrier-mediated mechanism into the BMEC, with energy supplied by Na+. However, l-histidine uptake at 0 degreesC was not completely inhibited, and it was reduced in the presence of an Na+-independent System-L substrate, BCH, suggesting facilitated diffusion (the Na+-independent process) by a carrier-mediated mechanism into the BMEC. l-histidine uptake in rat BMEC also appeared to be System-N mediated since uptake was inhibited by glutamine, aspargine and l-glutamic acid gamma-monohydroxamate. System-N mediated transport was not pH sensitive. d-histidine transport was also studied in rat BMEC. d-histidine transport by rat BMEC has similar characteristics to l-histidine. However, System-N transport did not play a role in d-histidine uptake. The uptake of l-histidine was also greater than that of the d-isomer, indicating the stereoselective uptake of histidine in rat BMEC.
Yamakami
J
J
Department of Pharmaceutics I, Tohoku College of Pharmacy, 4-1 Komatsushima 4-chome, Aoba-ku, Sendai 981-8558, Japan.
Sakurai
E
E
Sakurada
T
T
Maeda
K
K
Hikichi
N
N
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006639:Histidine / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D006639:Histidine