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.
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists; D005724:Ganglia / Q000187:drug effects / Q000378:metabolism; D007608:Kainic Acid / Q000037:antagonists & inhibitors*; D007865:Leeches / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate; D011759:Pyrrolidines / Q000037:antagonists & inhibitors*; D011956:Receptors, Cell Surface / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate
D000590:Amino Acid Chloromethyl Ketones; D018691:Excitatory Amino Acid Antagonists; D011759:Pyrrolidines; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate; D001224:Aspartic Acid; D016202:N-Methylaspartate; C041389:gamma-glutamylalanine chloromethyl ketone; D007608:Kainic Acid