PHENCYCLIDINE-BINDING SITES IN MOUSE CEREBRAL-CORTEX DURING DEVELOPMENT AND AGING - EFFECTS OF INHIBITORY AMINO-ACIDS

The binding of N-[1-(2-thienyl)cyclohexyl]-[H-3]piperidine ([H-3]TCP) to the phencyclidine-binding sites in the N-methyl-D-aspartate (NMDA) receptor complex-associated ion channel was characterized in cerebral cortical membranes from 3-day-old to 24-month-old mice. The binding wa s saturable, exhibiting only one binding component during the whole li fe-span studied. The maximal binding capacity B(max), calculated per p rotein content, decreased during postnatal development until 3 months of age, remaining thereafter constant in ageing mice, thus indicating the greatest availability of phencyclidine-binding sites in the immatu re cerebral cortex. The binding constant K(D) increased during the fir st postnatal week, remained thereafter unchanged and increased again d uring the second year of life, indicating a decreased affinity of the receptor sites for the ligand. The general properties of the binding; potentiation by glutamate and NMDA, as well as by glycine in a strychn ine-insensitive manner, prevailed during development and ageing, certa in of these effects being however less pronounced in the immature brai n. Taurine and beta-alanine stimulated TCP binding, acting probably at the glycine modulatory site. The actions of these inhibitory amino ac ids were weak and inconsistent when compared to that of glycine. Since NMDA receptors have been suggested to be involved in neuronal plastic ity and learning and memory processes, these modifications in the prop erties of cortical phencyclidine-binding sites might be of importance in the regulation of excitatory amino acid functions during developmen t and ageing.