Amino acid release from cerebral cortex in experimental acute liver failure, studied by in vivo cerebral cortex microdialysis.
Both increased gamma-aminobutyric acid (GABA)-ergic and decreased glutamatergic neurotransmission have been suggested relative to the pathophysiology of hepatic encephalopathy. This proposed disturbance in neurotransmitter balance, however, is based mainly on brain tissue analysis. Because the approach of whole tissue analysis is of limited value with regard to in vivo neurotransmission, we have studied the extracellular concentrations in the cerebral cortex of several neuroactive amino acids by application of the in vivo microdialysis technique. During acute hepatic encephalopathy induced in rats by complete liver ischemia, increased extracellular concentrations of the neuroactive amino acids glutamate, taurine, and glycine were observed, whereas extracellular concentrations of aspartate and GABA were unaltered and glutamine decreased. It is therefore suggested that hepatic encephalopathy is associated with glycine potentiated glutamate neurotoxicity rather than with a shortage of the neurotransmitter glutamate. In addition, increased extracellular concentration of taurine might contribute to the disturbed neurotransmitter balance. The observation of decreasing glutamine concentrations, after an initial increase, points to a possible astrocytic dysfunction involved in the pathophysiology of hepatic encephalopathy.
Bosman
D K
DK
J. van Gool Laboratory of Experimental Internal Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands.
Deutz
N E
NE
Maas
M A
MA
van Eijk
H M
HM
Smit
J J
JJ
de Haan
J G
JG
Chamuleau
R A
RA
D000208:Acute Disease; D000596:Amino Acids / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000032:analysis / Q000378:metabolism; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism*; D003956:Dialysis / Q000379:methods; D005971:Glutamates / Q000032:analysis / Q000378:metabolism; D005998:Glycine / Q000032:analysis / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013654:Taurine / Q000032:analysis / Q000378:metabolism; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000378:metabolism
D000596:Amino Acids; D005971:Glutamates; D014316:Tritium; D013654:Taurine; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D005998:Glycine