Differential inhibition by ferrous ions of [H-3]MK-801 binding to native N-methyl-D-aspartate channel in neonatal and adult rat brains

In vitro addition or pretreatment with greater than or equal to 1 mu M ferr ous chloride markedly inhibited in a concentration-dependent manner [H-3]di zocilpine (MK-801) binding to an open ion channel associated with the N-met hyl-D-aspartate (NMDA) receptor in rat brain synaptic membranes. The additi on of NMDA agonists invariably attenuated the inhibition of [H-3]MK-801 bin ding in hippocampal synaptic membranes previously treated with ferrous chlo ride, without significantly affecting that in cerebellar synaptic membranes . In the absence of spermidine, ferrous chloride was more potent in inhibit ing binding in the cerebral cortex and hippocampus in adult rats than in th ose in rats at 3 days after birth, while in the striatum [H-3]MK-801 bindin g was 10 times more sensitive to inhibition by added ferrous chloride in ne onatal rats than in adult rats. Addition of spermidine significantly attenu ated the potency of ferrous chloride to inhibit binding in the cerebral cor tex of adult rats. with facilitation of the inhibition in newborn rats. Mor eover, spermidine significantly reduced the inhibitory potency of ferrous c hloride in neonatal rat striatum. without markedly affecting that in adult rat striatum. These results suggest that ferrous ions may interfere with op ening processes of the native NMDA channel through molecular mechanisms pec uliar to neuronal development in a manner associated with the polyamine rec ognition domain. (C) 1999 Elsevier Science B.V. All rights reserved.