Hippocampal cells primed with quisqualate are depolarized by AP4 and AP6, ligands for a putative glutamate uptake site.

The glutamate analog 2-amino-4-phosphonobutyrate (AP4), which in control slices has little effect on Schaffer synaptic responses in hippocampal area CA1, reduces Schaffer responses in slices treated with quisqualate. We have shown that this effect of AP4 is associated with depolarization of CA1 neurons and a persisting small reduction in Schaffer response amplitude. 2-Amino-6-phosphonohexanoate also depressed Schaffer responses following priming with quisqualate, but 2-amino-7-phosphonoheptanoate did not. Treatment with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) or N-methyl-D-aspartate (NMDA) did not sensitize slices to AP4. The pharmacology of this 'priming effect' of quisqualate corresponds to that of a putative uptake site. We suggest the effects of AP4 (and AP6) result from exchange for previously accumulated quisqualate.