On the disposition of intrahippocampally injected kynurenic acid in the rat.

The disposition of kynurenic acid (KYNA), a tryptophan metabolite and broad spectrum antagonist at excitatory amino acid receptors, was studied following the unilateral intrahippocampal injection of 3H-KYNA in the rat. KYNA was rapidly cleared from the injected hippocampus. Similar decay curves were observed in several brain regions ipsi- and contralateral to the injection site as well as in serum and renal tissue. The radioactivity retained in tissue or excreted in urine for the first two hours after a 3H-KYNA injection was identified as unmetabolized KYNA. Moreover, direct measurement in hippocampal slices failed to provide evidence for the presence of specific cellular uptake mechanisms for KYNA. The present results do not support a neurotransmitter function for KYNA in the rat brain. However, they do not rule out a role of KYNA in the pathogenesis of neurodegenerative and seizure disorders.