Age-dependent effects of lead on [3H]MK-801 binding to the NMDA receptor-gated ionophore: in vitro and in vivo studies.
Lead (Pb2+) is a more potent inhibitor of [3H]MK-801 binding to rat neuronal membranes than Zn2+ and Mg2+. The inhibitory effects of Pb2+ appeared to be age-dependent since the IC50 was significantly lower in cortical membranes prepared from neonatal than from adult rats. The results also indicate that the hippocampus is more sensitive than the cerebral cortex since the Pb2+ IC50 was significantly lower in the hippocampus. These findings suggest developmental and regional brain heterogeneity to the inhibitory action of lead on [3H]MK-801 binding. Chronic in vivo exposure to Pb2+ resulted in the loss of [3H]MK-801 binding sites in the cerebral cortex of neonatal but not of adult rats. These lead-induced changes may influence developmental processes requiring NMDA receptor activation.
Guilarte
T R
TR
Department of Environmental Health Sciences, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, MD 21205.
Miceli
R C
RC
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D007854:Lead / Q000494:pharmacology*; D007855:Lead Poisoning / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D014316:Tritium; D015032:Zinc / Q000494:pharmacology
D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D007854:Lead; D016291:Dizocilpine Maleate; D008274:Magnesium; D015032:Zinc