Phencyclidine-binding sites in mouse cerebral cortex during development and ageing: effects of inhibitory amino acids.
The binding of N-[1-(2-thienyl)cyclohexyl]-[3H]piperidine ([3H]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 was saturable, exhibiting only one binding component during the whole life-span studied. The maximal binding capacity Bmax, calculated per protein 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 immature cerebral cortex. The binding constant KD increased during the first postnatal week, remained thereafter unchanged and increased again during 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 strychnine-insensitive manner, prevailed during development and ageing, certain of these effects being however less pronounced in the immature brain. Taurine and beta-alanine stimulated TCP binding, acting probably at the glycine modulatory site. The actions of these inhibitory amino acids were weak and inconsistent when compared to that of glycine. Since NMDA receptors have been suggested to be involved in neuronal plasticity and learning and memory processes, these modifications in the properties of cortical phencyclidine-binding sites might be of importance in the regulation of excitatory amino acid functions during development and ageing.
Saransaari
P
P
Tampere Brain Research Center, Department of Biomedical Sciences, University of Tampere, Finland.
Oja
S S
SS
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D005260:Female; D005998:Glycine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011869:Radioligand Assay; D017478:Receptors, Phencyclidine / Q000187:drug effects*; D013654:Taurine / Q000494:pharmacology*; D015091:beta-Alanine / Q000494:pharmacology*
D017478:Receptors, Phencyclidine; D015091:beta-Alanine; D013654:Taurine; D005998:Glycine