Title: Guanidinosuccinic acid, an endogene metabolite accumulating in uremic encephalopathy, is an NMDA receptor agonist in the CA1 region of rat hippocampal slices
Authors: Diltoer, M.
Lebrun, Ph.
Chowdhury, M.W.
De Ridder, Marjan
Engelborghs, S.
Williams, E.
D'Hooge, Rudi
De Deyn, P.P.
Colin, F.
Manil, J. #
Issue Date: 1995
Publisher: Springer-Verlag
Host Document: Pflügers Archiv: European journal of physiology vol:430 pages:149-149
Conference: FEPS congress edition:1 location:Maastricht, The Netherlands date:9-12 September 1995
Abstract: Guanidinosuccinic acid (GSA), an endogenous protein metabolite accumulating in renal insufficiency, ressembling L-aspartic acid and N-methyl-D-aspartate (NMDA) may play a role in the pathophysiology of uremic encephalopathy (memory loss and convulsions). We studied the effects of tonic applications (40') of GSA (from 31.25 µM to 1 mM) on the field potentials of the pyramidal cells of the CA1 region of rat hippocampal slices after electrical stimulation of the Shaffer collateral pathway at a frequency of 1/min. We found that GSA (from 62.5 10 125 µM) induced a dose dependent long-tem potentiation (GSA-LTP) and occluded the tetanic LTP considered to be an electrical correlate of memory at the cellular level. At concentrations of 250 and 500 µM, spontaneous activity and depression occur followed by the developpement of a GSA-LTP after washout. The application of 1 mM GSA did not allow any recuperation of the response and was toxic for most slices. All those effects were dose dependently antagonized by the NMDA-receptor antagonists D-AP5, MK801 and high extracellular Mg2+. The effects of GSA were amplified by 10 µM glycine and inhibited by the glycine-site antagonist 7 C1-kynurenic acid (50 µM). These results support the hypothesis that GSA is a NMDA agonist inducing a GSA-LTP facilitating convulsions and memory dysfunction in uremic encephalopathy.
ISSN: 0031-6768
Publication status: published
KU Leuven publication type: IMa
Appears in Collections:Laboratory for Biological Psychology
Microbial and Molecular Systems - miscellaneous
# (joint) last author

Files in This Item:

There are no files associated with this item.


All items in Lirias are protected by copyright, with all rights reserved.