Modulation of NMDA receptor by huperzine A in rat cerebral cortex.
OBJECTIVE
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 current was studied in acutely dissociated rat hippocampal pyramidal neurons using whole-cell recording. 2) The effect of Hup A on NMDA receptor binding was assessed using [3H] dizocilpine (Diz) binding assay in synaptic membrane preparation of rat cerebral cortex.


RESULTS
1) Hup A reversibly inhibited NMDA-induced current in a concentration-dependent manner with IC50 of 45.4 mumol.L-1. 2) Hup A inhibited the specific binding of [3H]MK-801 to extensively washed synaptic membrane of rat cerebral cortex in a concentration-dependent manner with IC50 of 0.5 (0.1-1.9) mumol.L-1 (n = 4). 3) L-Glutamate 10 mumol.L-1 markedly increased [3H] MK-801 binding. In the presence of L-glutamate, Hup A 0.001-0.1 mumol.L-1 caused a further increase of the binding, whereas Hup A 1-300 mumol.L-1 inhibited the binding in a concentration-dependent manner with IC50 of 12.3 (5.8-26.3) mumol.L-1 (n = 5).


CONCLUSIONS
Hup A acted as an antagonist of NMDA receptor in cerebral cortex in addition to its inhibitory effect on acetylcholinesterase.
Wang
X D
XD
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
Zhang
J M
JM
Yang
H H
HH
Hu
G Y
GY
D000470:Alkaloids; D000818:Animals; D002469:Cell Separation; D002540:Cerebral Cortex / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012717:Sesquiterpenes / Q000494:pharmacology*; D013570:Synaptic Membranes / Q000378:metabolism
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D012717:Sesquiterpenes; C050426:huperzine A; D016291:Dizocilpine Maleate