Glutamate transport regulation of renal glutaminase flux in
vivo.
Carter, Patsy, and Tomas Welbourne.
Department of Physiology, LSUMC, Shreveport, LA 71130,
APStracts 4:0123E, 1997.
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
14C-L-glutamine.
Ammonium production was measured as that released into the renal vein
plus that excreted while
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 minutes consistent with
interdiction of glutamate uptake. This reduction in the glutaminase
repressor was associated with
a 3-5 fold 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.
Received 1997 March 19; accepted in final form 1997 May 20
APS Manuscript Number E123-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 11 June 1997