Extracellular acidic sulfur-containing amino acids and gamma-glutamyl peptides in global ischemia: postischemic recovery of neuronal activity is paralleled by a tetrodotoxin-sensitive increase in cysteine sulfinate in the CA1 of the rat hippocampus.
An excessive activation of the excitatory amino acid system has been proposed as one possible mediator of the ischemia-induced delayed death of CA1 pyramidal cells in the hippocampus. Using dialytrodes in the CA1 of the rat, we have investigated multiple-unit activity and extracellular changes in acidic sulfur-containing amino acids and gamma-glutamyl peptides during ischemia (20-min, four-vessel occlusion) and during 8 h of reflow. Multiple-unit activity was abolished during ischemia and for the following 1 h, but then recovered, gradually reaching preischemic levels after 8 h of reflow. Extracellular cysteate, cysteine sulfinate, and gamma-glutamyltaurine increased (1.5- to threefold) during ischemia, and extracellular glutathione and gamma-glutamylaspartate plus gamma-glutamylglutamine increased during early reflow (two- to threefold). The recovery of neuronal activity at 4-8 h was paralleled by an increase in extracellular cysteine sulfinate (2.5-fold at 8 h of reflow). Perfusion with 10 microM tetrodotoxin at 8 h of reflow abolished the multiple-unit activity and reduced extracellular cysteine sulfinate. Considering the glutamate-like properties of cysteine sulfinate, the observed postischemic increase may be involved in the development of the delayed neuronal death.
Andiné
P
P
Institute of Neurobiology, University of Göteborg, Sweden.
Orwar
O
O
Jacobson
I
I
Sandberg
M
M
Hagberg
H
H
D000143:Acids / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism; D004563:Electrochemistry; D005110:Extracellular Space / Q000378:metabolism; D005973:Glutamine / Q000031:analogs & derivatives / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000502:physiology; D018377:Neurotransmitter Agents; D051381:Rats; D011919:Rats, Inbred Strains; D013455:Sulfur / Q000378:metabolism*; D013654:Taurine / Q000031:analogs & derivatives / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D000143:Acids; D000596:Amino Acids; D004151:Dipeptides; D018377:Neurotransmitter Agents; D005973:Glutamine; C047442:gamma-glutamylglutamine; C021030:gamma-glutamylaspartic acid; D013654:Taurine; D013779:Tetrodotoxin; D013455:Sulfur; C020903:glutaurine; D003545:Cysteine; C013461:cysteine sulfinic acid