Capek R, Esplin B
Department of Pharmacology and Therapeutics, McGill University, Montréal, QC, Canada.
Can J Physiol Pharmacol. 1997 Feb;75(2):158-63.
The influence of synaptic activity on the depression of N-methyl-D-aspartate (NMDA) receptor mediated synaptic responses by the noncompetitive blocker dizocilpine and the competitive antagonist CPP (3-((R)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid) was examined in the rat hippocampal slice preparation. In slices superfused by a Mg(2+)-free medium, both drugs, dizocilpine (2 to 100 microM) and CPP (0.2 to 10 microM), applied by perfusion, depressed the NMDA receptor mediated secondary population spikes (PSs) in the CA1 pyramidal cell layer. Repetitive stimulation (0.2 Hz, 5 min) greatly enhanced the depression produced by dizocilpine but was without any effect on the depression produced by CPP. In slices superfused with a normal medium, dizocilpine applied locally by pressure ejection (100 microM, 380 pL. 1 s) coupled with high-frequency stimulation (100 Hz, 1 s) prevented the appearance of multiple PSs in the subsequent 90-min period of perfusion with a Mg(2+)-free medium but was ineffective when applied without concomitant stimulation. These results indicate that the synaptic NMDA receptor mediated responses, similar to responses evoked by exogenous NMDA agonists, are depressed by dizocilpine in a use-dependent manner.
在大鼠海马脑片标本中，研究了突触活动对非竞争性拮抗剂地卓西平（MK-801）和竞争性拮抗剂CPP（3-((R)-2-羧基哌嗪-4-基)丙基-1-膦酸）抑制N-甲基-D-天冬氨酸（NMDA）受体介导的突触反应的影响。在无镁培养基灌流的脑片中，通过灌流施加的两种药物，地卓西平（2至100μM）和CPP（0.2至10μM），均抑制了CA1锥体细胞层中NMDA受体介导的继发性群体峰电位（PSs）。重复刺激（0.2Hz，5分钟）极大地增强了地卓西平产生的抑制作用，但对CPP产生的抑制作用没有任何影响。在正常培养基灌流的脑片中，通过压力喷射局部施加地卓西平（100μM，380pL，1s）并结合高频刺激（100Hz，1s），可在随后无镁培养基灌流的90分钟内阻止多个PSs的出现，但在无伴随刺激的情况下施加则无效。这些结果表明，突触NMDA受体介导的反应，类似于外源性NMDA激动剂诱发的反应，被地卓西平以使用依赖的方式抑制。
