Dizocilpine binding to cerebral cortical membranes from developing and ageing mice

Abstract

The binding of [ 3H]dizocilpine (MK-801) to the N-methyl-D-aspartate (NMDA)-gated ion channel was characterized in cerebral cortical membranes during the major portion of the mouse life-span (from 7-day- to 22-month-olds). The binding was saturable, consisting of only one component at all ages studied. The maximal binding capacity B max was very substantial in 14-day-old mice when compared to adults (3-month-olds), decreasing there-after during ageing. The binding constant K D remained unchanged during development and increased only slightly in aged mice. Glutamate and glycine potentiated dizocilpine binding concentration-dependently. Their efficacy varied markedly with age. Both glutamate and glycine had considerably less effect on the immature cerebral cortex and in the oldest group of mice (22-month-old) than in young adults. The marked increase in dizocilpine binding sites at the age of 2 weeks coincides with the previously reported transient increase in NMDA binding sites in the cerebral cortex. The weak potentiation of dizocilpine binding by glutamate and glycine in the immature brain could be a factor which protects neurons during this period from excitotoxicity and increased susceptibility to seizures induced by acidic amino acids. The decrease in the number of dizocilpine binding sites during ageing could result partly from the loss of cortical neurons.