ZN2-3] MK-801 BINDING IS DIFFERENT IN MOUSE-BRAIN AND SPINAL-CORD - EFFECT OF GLYCINE AND GLUTAMATE( INHIBITION OF [H)

Zn2+ inhibits NMDA-type excitatory amino acid activity by a non-compet itive action. Based on regional differences in the central nervous sys tem (CNS) in binding characteristics of 0,11-dihydro-5H-dibenzo[a,d]cy clohepten-5,10-imine maleate ([H-3]MK-801) and other non-competitive a ntagonists of NMDA used to label open channels in the receptor complex , we compared the inhibitory influence of Zn2+ on [H-3]MK-801 binding in whole mouse brain and spinal cord membranes. Radioligand binding te chniques were used in the presence and absence of maximally effective concentrations of glycine and glutamate. Using extensively washed memb ranes without exogenous glycine and glutamate, Zn2+ was found to be a weaker inhibitor of the [H-3]MK-801-labeled site in the spinal cord th an in the whole brain. In contrast, exogenous glycine and glutamate de creased the inhibitory effect of Zn2+ in the brain but dramatically in creased the inhibitory effect of Zn2+ in the spinal cord. Thus the inh ibitory effect of Zn2+ in the spinal cord appears to be magnified by g lutamatergic and glycinergic activity while that in the brain is not. The different actions of Zn2+ may be attributable to the differential distribution of NMDA receptor subunits in the mouse brain and spinal c ord. (C) 1997 Elsevier Science B.V.