Preventive effects of exogenous phospholipases on inhibition by ferrous ions of [3H]MK-801 binding in rat brain synaptic membranes.

Prior treatment with ferrous chloride led to marked inhibition of 3H-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801) binding to an open ion channel associated with the N-methyl-D-aspartate (NMDA) receptor in a concentration-dependent manner at concentrations of higher than 1 microM in rat brain synaptic membranes. Both phospholipases A2 and C significantly prevented the inhibition when treated before the treatment with ferrous chloride, while neither superoxide dismutase nor alpha-tocopherol affected the inhibition even when treated simultaneously with ferrous chloride. Of various saturated and unsaturated free fatty acids, moreover, both oleic and arachidonic acids exclusively decreased the potency of ferrous chloride to inhibit binding when membranes were first treated with fatty acids, followed by the second treatment with ferrous chloride. These results suggest that membrane phospholipids may be at least in part responsible for interference by ferrous ions with opening processes of the native NMDA channel through molecular mechanisms associated with the liberation of unsaturated free fatty acids in rat brain.