L-alpha-aminoadipate inhibits kynurenate synthesis in rat brain hippocampus and tissue culture.
Intracerebral administration of L-alpha-aminoadipic acid (L-AAA) at 500 mg/kg body weight to rats caused a complex behavioral change with sporadic wet-dog shakes. Animals developed severe limbic seizures between 1 and 6 h after L-AAA injection, characterized by generalized convulsions. Twenty days after L-AAA injection kynurenine aminotransferase (KAT) activity measured in hippocampal brain tissue slices prepared with a McIlwain chopper at 30 microns showed a significant 43% decrease. Subcutaneous injection of kynurenine at 500 mg/kg showed a 63% increase in KAT activity twenty days later. This increase was offset by a concomitant administration of 500 mg/kg L-AAA stereotaxically on day one. In astrocyte culture kynurenic acid synthesis is inhibited by L-AAA and L-pipecolic acid. The possible involvement of kynurenic acid in the modulation of neuronal degeneration is discussed.
Chang
Y F
YF
Department of Oral and Craniofacial Biological Sciences, University of Maryland Dental School, Baltimore 21201, USA.
Cauley
R K
RK
Chang
J D
JD
Rao
V V
VV
D015074:2-Aminoadipic Acid / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007736:Kynurenic Acid / Q000378:metabolism*; D008845:Microinjections; D009924:Organ Culture Techniques; D010875:Pipecolic Acids / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced; D013238:Stereotaxic Techniques
D010875:Pipecolic Acids; D015074:2-Aminoadipic Acid; D007736:Kynurenic Acid; C031345:pipecolic acid