(Aminooxy)acetic acid → Kynurenine

Participants

Reaction Steps

In order to establish that the kynurenic acid measured in striatal ECF was synthesized in the CNS rather than transported into the CNS from the periphery, we examined the ability of aminooxyacetic acid (AOAA), an established inhibitor of kynurenine transaminase, to inhibit the kynurenic acid surge produced by peripheral infusion of L-kynurenine. We designed a model with internal controls to negate the effects of variable L-kynurenine absorption from the periphery. Dialysis probes were implanted bilaterally into the striata of five rats. Initially, both probes were infused with artificial ECF. After 1.5 hours of pre-baseline perfusion, three consecutive 30 minute baseline fractions were collected from each probe. After the last fraction was collected, artificial ECF containing either 1.0 mM (N=3 rats) or 2.0 mM (N=2 rats) AOAA was perfused through one probe, while the contralateral probe was perfused with artificial ECF alone, as a control. Both probes were perfused for 1.5 hours (three consecutive 30 minute fractions). After the last fraction was collected L-kynurenine (75 mg kg−1) was administered peripherally via an intraperitoneal route. Dialysis fractions were then collected, at 30 minute intervals, for the next 3.0 hours. Ipsi-lateral (AOAA perfused) and contralateral (control) fractions were analyzed for kynurenic acid.

Provenance & Evidence