Effects of the New Anti-Ulcer Drug Ecabet Sodium (TA-2711) on Pepsin Activity I. Inactivation of Enzyme Protein

We attempted to observe the dentate gyrus field potential evoked by low-frequency stimulation of the perforant path in Mg(2+)-free medium and identify the N-methyl-D-aspartate (NMDA) receptor-mediated synaptic potential using rat hippocampal slices. When perfusing solution was changed from normal medium (1.3 mM Mg2+) to Mg(2+)-free medium, the evoked potential was greatly increased and secondary population spikes appeared following a primary population spike. The evoked potential recorded in Mg(2+)-free medium was only partly blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist. The CNQX-resistant component of the evoked potential in Mg(2+)-free medium was completely abolished by 30 microM DL-2-amino-5-phosphonovalerate, a NMDA receptor antagonist, indicating that the NMDA receptor-mediated synaptic response can be isolated by masking the non-NMDA receptor-mediated component of the evoked potential under the Mg(2+)-free condition. The isolated NMDA receptor-mediated synaptic potential was also blocked by 7-chlorokynurenate, an antagonist at the glycine site of the NMDA receptor, and restored by the concomitant presence of glycine. Observation of pharmacologically isolated NMDA receptor-mediated synaptic potential is a simple and good method for studying the direct effects of drugs on NMDA receptor-mediated responses.