DEVELOPMENTAL MODULATION OF CYSTEINE CONJUGATE BETA-LYASE GLUTAMINE TRANSAMINASE K/KYNURENINE AMINOTRANSFERASE MESSENGER-RNA IN RAT-BRAIN/

Cysteine conjugate beta-lyase/glutamine transaminase K/kynurenine amin otransferase (CS-lyase/GTK/KAT) is a tri-functional enzyme found in se veral organs, including the brain. Kynurenine aminotransferase is impo rtant in tryptophan metabolism in the CNS, producing kynurenic acid, a NMDA receptor antagonist and neuroprotective. Tryptophan not metaboli sed via kynurenine aminotransferase may form quinolinic acid, a NMDA r eceptor agonist and neurotoxin. Kynurenic acid co-treatment blocks qui nolinic acid induced lesions in the CNS in rat. In many conditions exh ibiting neurodegeneration (i.e. Huntington's, Parkinsonism, Down's syn drome) quinolinic acid and/or kynurenic acid concentrations are altere d, suggesting the ratio of these chemicals may be important in neurode generation. We have investigated the developmental modulation of CS-ly ase/GTK/KAT mRNA in rat brain. CS-lyase/GTK/KAT mRNA was measured in 1 4, 21, 28, 35, 42 day post-natal and adult rats. While many regions de monstrated a steady increase to adult levels, two other profiles were seen. Five regions rapidly reached adult levels of the mRNA, while two peaked above the adult level before falling back. This provides evide nce that expression of the CS-lyase/GTK/KAT gene is physiologically mo dulated, and provides the basis for further investigation into the mec hanism of control. Artificial modulation could possibly be used to alt er levels of the neuroprotectant kynurenic acid in neurodegeneration.