Glutamate transport regulation of renal glutaminase flux in vivo

被引:8
作者
Carter, P [1 ]
Welbourne, T [1 ]
机构
[1] LOUISIANA STATE UNIV, MED CTR, DEPT PHYSIOL, SHREVEPORT, LA 71130 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 1997年 / 273卷 / 03期
关键词
metabolic regulation; C-14]glutamine conversion to glutamate; ammonium production; D-aspartate; glutamine uptake; cellular glutamate;
D O I
10.1152/ajpendo.1997.273.3.E521
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We proposed that glutamate transport into cultured kidney cells represses cellular glutaminase activity and hence regulates glutamine utilization. To test this putative regulatory mechanism in vivo, glutamine uptake and conversion to glutamate as well as ammonium production were measured in the intact functioning rat kidney. Glutamine uptake was determined as net removal, arteriovenous concentration difference times renal plasma flow, and also as unidirectional uptake from the fractional extraction of tracer L-[C-14]glutamine. Ammonium production was measured as that released into the renal vein plus that excreted, and intracellular glutamine conversion to glutamate was assessed from the rise in cortical glutamate radiolabel specific activity. Cellular glutamate content was reduced 50-60% by infusing D-aspartate (a high-affinity glutamate transporter inhibitor) over 30 min, consistent with interdiction of glutamate uptake. This reduction in the glutaminase repressor was associated with a three-to fivefold increase in glutamine uptake and intracellular conversion to glutamate and ammonium. These results are consistent with and predictable from our previous in vitro model and point to an important role for this regulatory mechanism in the intact functioning organ.
引用
收藏
页码:E521 / E527
页数:7
相关论文
共 31 条
  • [1] ARRIZA JL, 1994, J NEUROSCI, V14, P5559
  • [2] BERGMAN EN, 1986, FASEB J, V45, P2277
  • [3] BOS K, 1985, CLIN CHIM ACTA, V752, P205
  • [4] RENAL AMMONIUM PRODUCTION - UNE VUE CANADIENNE
    BROSNAN, JT
    LOWRY, M
    VINAY, P
    GOUGOUX, A
    HALPERIN, ML
    [J]. CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 1987, 65 (04) : 489 - 498
  • [5] LOCATION OF GLUTAMINE-SYNTHETASE WITHIN RAT AND RABBIT NEPHRON
    BURCH, HB
    CHOI, S
    MCCARTHY, WZ
    WONG, PY
    LOWRY, OH
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1978, 82 (02) : 498 - 505
  • [6] DAMIAN A, 1970, AM J PHYSIOL, V218, P1248
  • [7] PNH3 OF RENAL TUBULAR CELLS
    DENIS, G
    PREUSS, H
    PITTS, R
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1964, 43 (04) : 571 - &
  • [8] FERNSTROM JD, 1991, LIFE SCI, V10, P813
  • [9] Frindt G, 1988, Contrib Nephrol, V63, P114
  • [10] GAZZOLA GC, 1981, J BIOL CHEM, V256, P6054