EVIDENCE FOR CARRIER-MEDIATED TRANSPORT OF GLUTATHIONE ACROSS THE BLOOD-BRAIN-BARRIER IN THE RAT

被引:153
作者
KANNAN, R
KUHLENKAMP, JF
JEANDIDIER, E
TRINH, H
OOKHTENS, M
KAPLOWITZ, N
机构
[1] WADSWORTH VET ADM MED CTR,LIVER RES LAB,LOS ANGELES,CA 90073
[2] UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90025
关键词
amino acids; brain uptake index; gamma-glutamyltranspeptidase; oxidized glutathione (GSSG); reduced glutathione (GSH);
D O I
10.1172/JCI114666
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Information on the origin of brain glutathione and the possibility of its transport from blood to brain is limited. We found a substantial uptake of 35S-labeled glutathione by the rat brain using the carotid artery injection technique. The brain uptake index of glutathione with and without an irreversible gamma-glutamyl transpeptidase inhibitor, acivicin, was similar. No significant differences in the regional uptake of labeled glutathione were found in rats pretreated with acivicin. The brain uptake index of tracer glutathione was similar to that of cysteine tracer and was lower than that of phenylalanine. The transport of oxidized glutathione (glutathione disulfide) across the blood-brain barrier was not significantly different from that of sucrose, an impermeable marker. Brain radioactivity 15 s after carotid artery injection of labeled glutathione to rats pretreated with acivicin was predominantly in the form of glutathione. The in vivo glutathione uptake was saturable with an apparent K(m) of 5.84 mM. Amino acids, amino acid analogues, and other compounds [cysteine, phenylalanine, glutathione disulfide, gamma-glutamylglutamate, gamma-glutamyl p-nitroanilide, 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid (BCH)] did not affect glutathione transport. Our data suggest that glutathione is transported across the blood-brain barrier by a saturable and specific mechanism.
引用
收藏
页码:2009 / 2013
页数:5
相关论文
共 35 条
  • [1] ABBOTT WA, 1984, J BIOL CHEM, V259, P15593
  • [2] GLUTATHIONE MONOETHYL ESTER - PREPARATION, UPTAKE BY TISSUES, AND CONVERSION TO GLUTATHIONE
    ANDERSON, ME
    POWRIE, F
    PURI, RN
    MEISTER, A
    [J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1985, 239 (02) : 538 - 548
  • [3] GLUTATHIONE METABOLISM AT THE BLOOD CEREBROSPINAL-FLUID BARRIER
    ANDERSON, ME
    UNDERWOOD, M
    BRIDGES, RJ
    MEISTER, A
    [J]. FASEB JOURNAL, 1989, 3 (13) : 2527 - 2531
  • [4] BANNAI S, 1980, J BIOL CHEM, V255, P2372
  • [5] BUTLER J, 1974, ANAL BIOCHEM, V75, P674
  • [6] CORNFORD EM, 1978, ENDOCRINOLOGY, V103, P1287
  • [7] DAWSON AR, 1984, EUR J BIOCHEM, V13, P439
  • [8] BLOOD-BRAIN BARRIER AND PEPTIDES
    ERMISCH, A
    RUHLE, HJ
    LANDGRAF, R
    HESS, J
    [J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1985, 5 (03) : 350 - 357
  • [9] FARISS MW, 1987, METHOD ENZYMOL, V143, P101
  • [10] GLUTATHIONE - INTERORGAN TRANSLOCATION, TURNOVER, AND METABOLISM
    GRIFFITH, OW
    MEISTER, A
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1979, 76 (11) : 5606 - 5610