Abstract
JS‐11‐37 is a novel phencyclindine (PCP) analog that was designed to act as selective NMDA receptor antagonist. Since NMDA receptor antagonists can modulate excitatory neurotransmitter release (Ohia, et al., Neurochem. Res. 25:853, 2000), in the present study, we investigated the effect of JS‐11‐37 on potassium (K+)‐ and glutamate‐induced glutamate release (using [3H]D‐aspartate as marker) from isolated bovine retina. Tissues were incubated in oxygenated Krebs solution containing 200nM of [3H]D‐aspartate for 60 minutes and then prepared for studies of neurotransmitter release using the Superfusion method. Release of [3H]D‐aspartate was elicited by iso‐osmotic concentration of K+ (50mM) at S1 and either K+ (50mM) or L‐glutamate (100 μM) at S2. JS‐11‐37 (1 nM to 1 μM) attenuated both K+(50mM)‐induced and glutamate‐induced [3H]D‐aspartate release in a concentration‐dependent manner. For instance, at 1 nM, JS‐11‐37 inhibited K+‐induced [3H]D‐aspartate release by 31% (P<0.001). The IC30 (effective concentration of drug that caused 30% inhibition of glutamate‐induced release) value obtained for JS‐11‐37 (0.85μM ± 0.01) was comparable to that obtained for the NMDA receptor antagonist, AP‐5 (1.23μM ± 0.66). In conclusion, JS‐11‐37 can elicit an inhibitory effect on both K+‐ and glutamate‐evoked [3H]D‐aspartate release from isolated bovine retinae, presumably via an effect on NMDA receptors.