title: Stereoselective transport of histidine in rat lung microvascular endothelial cells.
abstract: The transport characteristics of L- and D-histidine through the blood-lung barrier were studied in cultured rat lung microvascular endothelial cells (LMECs). L-Histidine uptake was a saturable process. The addition of metabolic inhibitors [2,4-dinitrophenol (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 initial L-histidine uptake rate was reduced by the substitution of Na(+) with choline chloride and choline bicarbonate in the incubation buffer. The system N substrate, L-glutamic acid gamma-monohydroxamate, also inhibited uptake of L-histidine. However, system N-mediated transport was not pH sensitive. These results demonstrated that L-histidine is actively taken up by a system N transport mechanism into rat LMECs, with energy supplied by Na(+). Moreover, the Na(+)-independent system L substrate, 2-amino-2-norbornanecarboxylic acid (BCH), had an inhibitory effect on L-histidine uptake in Na(+) removal, indicating facilitated diffusion by a Na(+)-independent system L transport into the rat LMECs. These results provide evidence for there being at least two pathways for L-histidine uptake into rat LMECs, a Na(+)-dependent system N and Na(+)-independent system L process. On the other hand, the uptake of D-histidine into rat LMECs was not reduced by the addition of DNP, rotenone, or ouabain, or by Na(+) replacement. Although the uptake of D-histidine was reduced in the presence of BCH, the addition of L-glutamic acid gamma-monohydroxamate did not significantly decrease uptake of D-histidine. These results suggest that the uptake of D-histidine by rat LMECs has different characteristics compared with its isomer, L-histidine, indicating that system N transport did not involve D-histidine uptake.
authors: Department of Pharmaceutics I, Tohoku Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan. sakauraie@tohoku-pharm.ac.jp
authors: Eiichi
authors: E
authors: Sakurai
authors: Tomoya
authors: T
authors: Sakurada
authors: Yoshinori
authors: Y
authors: Ochiai
authors: Jun
authors: J
authors: Yamakami
authors: Yorihisa
authors: Y
authors: Tanaka
mesh_terms: D026905:Amino Acid Transport Systems / Q000187:drug effects / Q000378:metabolism*; D000598:Amino Acids, Cyclic / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006639:Histidine / Q000378:metabolism* / Q000493:pharmacokinetics; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors; D008168:Lung / Q000098:blood supply* / Q000166:cytology; D008297:Male; D008833:Microcirculation / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008968:Molecular Conformation; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity / Q000187:drug effects / Q000502:physiology; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D026905:Amino Acid Transport Systems; D000598:Amino Acids, Cyclic; D004791:Enzyme Inhibitors; D014475:Uncoupling Agents; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D006639:Histidine; D010042:Ouabain; D012964:Sodium; D006640:Histidine Decarboxylase