Modulation of NMDA receptor by huperzine A in rat cerebral cortex

AIM: To investigate the effects of huperzine A (Hup A) on NMDA receptors in rat cerebral cortex. METHODS: 1) The effect of hup A on NMDA-induced curre nt was studied in acutely dissociated rat hippocampal pyramidal neurons usi ng whole-cell recording. 2) The effect of Hup A on NMDA receptor binding wa s assessed using [H-3] dizocilpine (Diz) binding assay in synaptic membrane preparation of rat cerebral cortex. RESULTS: I) Hup A reversibly inhibited NMDA-induced current in a concentration-dependent manner with IC50 of 45.4 mu mol.L-1. 2) Hup A inhibited the specific binding of [H-3]MK-801 to exte nsively washed synaptic membrane of rat cerebral cortex in a concentration- dependent manner with ICS, of 0.5 (0.1 - 1.9) mu mol.L-1(n = 4). 3) L-Gluta mate 10 mu mol.L-1 markedly increased [H-3] MK-801 binding. In the presence of L-glutamate, Hup A 0.001 - 0.1 mu mol.L-1 caused a further increase of the binding, whereas Hup A 1 - 300 mu mol.L-1 inhibited the binding in conc entration-dependent manner with IC50 of 12.3 (5.8 - 26.3) mu mol.L-1(n = 5) . CONCLUSION: Hup A acted as an antagonist of NMDA receptor in cerebral cor tex in addition to its inhibitory effect on acetylcholinesterase.