PHENYLGLYCINES CAN EVOKE QUISQUALATE-PRIMED DEPOLARIZATIONS IN RAT CINGULATE CORTEX - AN EFFECT ASSOCIATED WITH [H-3] DL-AP4 UPTAKE

Depolarization could be evoked in slices of rat cingulate cortex by th e normally non-excitatory compound L-2-amino-4-phosphonobutyrate (L-AP 4) if the slices had been sensitized by exposure to quisqualate. The m agnitude of the response to L-AP4 was dependent on the concentrations of both L-AP4 and quisqualate and was inhibited by alpha-amino-3-hydro xy-5-methyl-4-isoxazole propionate receptor antagonism. A series of ph enylglycine analogues were capable of evoking similar dose-dependent d epolarizations in the rat cingulate cortex following quisqualate sensi tization, the most potent being (S)-4-carboxy-3-hydroxyphenylglycine. If the superfusate collected during application of (S)-4-carboxy-3-hyd roxyphenylglycine to a quisqualate-sensitized slice was administered t o a slice not previously exposed to quisqualate, a small depolarizatio n was obtained. All the compounds shown to be capable of evoking the q uisqualate-sensitized response showed affinity for the L-AP4 uptake si te whilst having no affinity at ionotropic glutamate receptors and dif ferent profiles of activity at metabotropic glutamate receptors. None of the compounds was active at the metabotropic glutamate 4a receptor. There was a statistically significant correlation between a compound' s effectiveness in inhibiting [H-3]DL-AP4 uptake into rat cortical syn aptosomes and its potency in evoking quisqualate-sensitized depolariza tion. It is concluded that this response may be the result of hetero-e xchange between L-AP4 ligands and quisqualate.