gamma-glutamyl peptides and related amino acids in rat hippocampus in vitro: Effect of depolarization and gamma-glutamyl transpeptidase inhibition

被引:11
作者
Li, XY [1 ]
Orwar, O [1 ]
Revesjo, C [1 ]
Sandberg, M [1 ]
机构
[1] UNIV GOTHENBURG,INST ANAT & CELL BIOL,S-41390 GOTHENBURG,SWEDEN
关键词
D O I
10.1016/0197-0186(95)00148-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The concentrations of gamma-glutamylglutamate, gamma-glutamylglutamine, gamma-glutamylcysteine, glutamate, aspartate, glutamine, cyst(e)ine and glutathione (including disulfides) were determined by HPLC analysis of both the tissue and the surrounding medium of incubated rat hippocampal slices. High potassium concentrations (50 mM; 2 x 4 min) increased the medium concentration of gamma-glutamylglutamate (maximal net efflux 0.07+/-0.06 pmol/mg protein/min; n = 8+/-SD) with a relative time delay compared to the increase in glutamate (maximal net efflux 264+/-88 pmol/mg protein/min). Release of gamma-glutamylcysteine, the glutathione precursor, demonstrated an immediate response and gradually approached prestimulus levels (maximal net efflux 0.36+/-0.13 pmol/mg protein/min). Addition of acivicin (0.2 mM), a gamma-glulamyl transpeptidase (EC 2.3.2.2.) blocker, during preincubation for 45 min reduced the tissue concentrations (pmol/mg protein) of gamma-glutamylglutamate (19.4+/-8.2 (control) vs. 5.8+/-3.6 (+acivicin)), gamma-glutamylglutamine (40.3+/-6.7 vs. 25.7+/-4.2 pmol/mg protein), glutamine (9.9+/-2.0 vs. 4.6+/-1.2 nmol/mg protein) and cysteine (1.0+/-0.2 vs. 0.56+/-0.18 nmol/mg protein). Incubation with acivicin (0.2 mM) reduced the net efflux of gamma-glutamylglutamine (0.79+/-0.19 vs. 0.21+/-0.07 pmol/mg protein/min) whereas that of the glutathione was increased (4.7+/-1.0 vs. 20+/-3 pmol/mg protein/min). The medium concentrations of glutamate in both low and high potassium were unaffected by acivicin, while the high potassium induced increase in gamma-glutamylglutamate was blocked. The results demonstrate differential efflux patterns of gamma-glutamyl dipeptides from brain slices and show that in vitro the activity of gamma-glutamyl transpeptidase regulates extracellular concentrations of glutathione, gamma-glutamylglutamine and gamma-glutamylglutamate. Copyright (C) 1996 Elsevier Science Ltd.
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页码:121 / 128
页数:8
相关论文
共 63 条
[1]   SELECTIVE MODULATION OF NMDA RESPONSES BY REDUCTION AND OXIDATION [J].
AIZENMAN, E ;
LIPTON, SA ;
LORING, RH .
NEURON, 1989, 2 (03) :1257-1263
[2]  
ALLEN L, 1980, RES COMMUN CHEM PATH, V27, P175
[3]   TRANSPORT AND DIRECT UTILIZATION OF GAMMA-GLUTAMYLCYST(E)INE FOR GLUTATHIONE SYNTHESIS [J].
ANDERSON, ME ;
MEISTER, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (03) :707-711
[4]   GLUTATHIONE METABOLISM AT THE BLOOD CEREBROSPINAL-FLUID BARRIER [J].
ANDERSON, ME ;
UNDERWOOD, M ;
BRIDGES, RJ ;
MEISTER, A .
FASEB JOURNAL, 1989, 3 (13) :2527-2531
[6]   GLUTAMATE UPTAKE BY BRAIN SLICES AND ITS RELATION TO DEPOLARIZATION OF NEURONS BY ACIDIC AMINO-ACIDS [J].
BALCAR, VJ ;
JOHNSTON, GA .
JOURNAL OF NEUROBIOLOGY, 1972, 3 (04) :295-&
[7]   THE TIME COURSE OF GLUTAMATE IN THE SYNAPTIC CLEFT [J].
CLEMENTS, JD ;
LESTER, RAJ ;
TONG, G ;
JAHR, CE ;
WESTBROOK, GL .
SCIENCE, 1992, 258 (5087) :1498-1501
[8]  
COOPER JDH, 1987, METHOD ENZYMOL, V143, P141
[10]   OXIDIZED GLUTATHIONE MODULATES N-METHYL-D-ASPARTATE-INDUCED AND DEPOLARIZATION-INDUCED INCREASES IN INTRACELLULAR CA2+ IN CULTURED RAT FOREBRAIN NEURONS [J].
GILBERT, KR ;
AIZENMAN, E ;
REYNOLDS, IJ .
NEUROSCIENCE LETTERS, 1991, 133 (01) :11-14