EFFECT OF N-G-NITRO-L-ARGININE ON AGE-RELATED-CHANGES OF GLUTAMATE-RECEPTOR SYSTEMS AND IMMUNOPHILIN IN RATS

We investigated the effects of age and N-G-nitro-L-arginine methyl est er (L-NAME) on glutamate receptor systems and immunophilin in Fischer rat brain using receptor autoradiography. [H-3]MK-801, [H-3]glycine, s odium-dependent [H-3]D-asparate and [H-3]FK-506 were used to label N-m ethyl-D-aspartate (NMDA) receptors, glycine receptors, excitatory amin o acid transport sites and FK-506 binding proteins (FKBP), respectivel y. [H-3]Glycine and sodium-dependent [H-3]D-aspartate binding signific antly reduced in the cerebral cortex, striatum, hippocampus, thalamus, substantia nigra and cerebellum of aged (24-month-old) rats in compar ison with adult (6-month-old) animals. In contrast, [H-3]MK-801 and [H -3]FK-506 binding showed no significant changes in most brain regions of aged rats. Intraperitoneal chronic treatment with L-NAME (5 mg/kg, once a day for 4 weeks) showed no conspicuous changes in these binding sites in most brain areas of aged rats. in the cerebellum however; th is treatment showed a significant change in both [H-3]MK-801 and sodiu m-dependent [H-3]D-aspartate binding in aged mrs. These results demons trate that glycine receptors and excitatory amino acid transport sites are more susceptible to aging processes than NMDA receptors and FKBP. Furthermore, our findings may suggest a possible role of nitric oxide in the regulation of cerebellum during aging processes.