Intracerebral administration of L-kynurenine decreases N-methyl-D-aspartate receptor-mediated production of cGMP in the cerebellum and hippocampus of unanaesthetized rats subjected to transcerebral microdialysis.
The effects of intracerebral administration of L-kynurenine (L-KYN) on the N-methyl-D-aspartate (NMDA) receptor-mediated, nitric oxide (NO)-dependent cGMP responses have been studied in vivo in the cerebellum and hippocampus of freely-moving rats subjected to transcerebral microdialysis. Administration of exogenous NMDA in the cerebellum through the dialysis probe evoked a 3-fold increase of basal extracellular levels of cGMP that was concentration-dependently reduced by co-infusion of L-KYN. In the hippocampus, local administration of cyclothiazide caused a significant enhancement of the cyclic nucleotide dialysate concentrations that was accompanied by behavioural manifestations characteristic of preconvulsive states. Co-infusion of L-KYN largely decreased the neurochemical effects of cyclothiazide and completely prevented the appearance of the behavioural episodes. It is concluded that administration of L-KYN by increasing endogenous kynurenic acid concentrations might exert neuroprotective and anticonvulsive effects through blockade of the NMDA receptor/NO/cGMP pathway.
Varnier
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G
Dipartimento di Medicina Sperimentale, Università di Genova, Genova, Italy.
Fedele
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Marchi
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Raiteri
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D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D006152:Cyclic GMP / Q000096:biosynthesis*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007737:Kynurenine / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D016194:Receptors, N-Methyl-D-Aspartate; D007737:Kynurenine; D006152:Cyclic GMP