Pb2+ inhibits NMDA receptor function at high and low affinity sites: developmental and regional brain expression

Lead (Pb2+) is a potent inhibitor of the NMDA receptor complex. In the present study we have measured high and low affinity components of NMDA receptor inhibition by Pb2+ using [3H]-MI-801 binding as a biochemical indicator of NMDA receptor function. The inhibitory effects of Pb2+ were dependent on the age of the rat and the brain region analyzed. The number of [3H]-MK-801 binding sites associated with the high and low affinity sites of Pb2+ inhibition in the hippocampus increased as a function of age, peaking at postnatal day 28 and 21, respectively. In the cerebellum, a steady decrease in the number of both types of Pb(2+)-sensitive [3H]-MK-801 binding sites was measured from postnatal day 1 to adulthood. High and low affinity Pb(2+)-sensitive [3H]-MK-801 binding sites were measured in the cerebral cortex in early development, but the resolution of the two sites was not possible after postnatal day 14. The Pb2+ sensitivity of the NMDA receptor complex also appeared to be regulated developmentally.