Effect of pesticides on kynurenic acid production in rat brain slices.

ABSTRACT

Kynurenic acid (KYNA) is a broad spectrum antagonist of ionotropic glutamate receptors, preferentially active at the strychnine-insensitive glycine allosteric site of the N-methyl-D-aspartate (NMDA) receptor, and a noncompetitive antagonist of alpha7 nicotinic receptor. Animal studies showed that it possesses anticonvulsant and neuroprotective properties. Its involvement in the pathophysiology of various brain disorders was suggested. In this study, the effect of pesticides on KYNA production in brain cortical slices was investigated. Pyrethroids, deltamethrin and fenpropathrin significantly lowered KYNA production. Methomyl, bensultap, fipronil, diquat and MCPA were ineffective in this regard. In view of this data, the inhibition of KYNA synthesis appear to merit further investigation as a potential factor contributing to the toxicology of pyrethroids.