The halomethylketone derivative L-Glu-gamma-DL-Ala-CH2Cl and N-methyl-D-aspartate as selective antagonists against L-glutamate and kainate excitation respectively on Retzius cells of the leech, Hirudo medicinalis.

Intracellular recordings were made from leech Retzius cells. The action of a range of putative antagonists was examined on the excitatory responses to dicarboxylic amino acids which were applied via a diffusion electrode. The halomethylketone derivative, L-Glu-gamma-DL-Ala-CH2Cl was found to block preferentially the L-glutamate response compared to the kainate response. This compound had no effect on the response to carbachol. N-Methyl-D-aspartate was found to block the response to kainate while having no effect on the responses to L-glutamate, ibotenate or carbachol. This compound had no direct action on the cell. N-Methyl-D-aspartic acid also reduced the excitatory responses to methyltetrahydrofolate and 3- carboxymethylpyrrolidine -2,4-dicarboxylic acid ( CMPDA ). gamma-D-Glutamyl-amino methyl-sulphonate ( GAMS ), while partially blocking the action of kainate, had no effect on the response to ibotenate. gamma-D-Glutamylglycine was found to reduce the response to L-glutamate, ibotenate, kainate, quisqualate and CMPDA . CMPDA , a tricarboxylic acid derivative of kainate, was found to be approximately equipotent with kainate on leech Retzius cells. This compound was partially blocked by N-methyl-D-aspartate. The present study demonstrates that it is possible to differentially block L-glutamate and kainate on leech Retzius cells and indicates that they are acting on separate components of the membrane.