Effect of NG-nitro-L-arginine on age-related changes of glutamate receptor systems and immunophilin in rats.
We investigated the effects of age and NG-nitro-L-arginine methyl ester (L-NAME) on glutamate receptor systems and immunophilin in Fischer rat brain using receptor autoradiography. [3H]MK-801, [3H]glycine, sodium-dependent [3H]D-aspartate and [3H]FK-506 were used to label N-methyl-D-aspartate (NMDA) receptors, glycine receptors, excitatory amino acid transport sites and FK-506 binding proteins (FKBP), respectively. [3H]Glycine and sodium-dependent [3H]D-aspartate binding significantly reduced in the cerebral cortex, striatum, hippocampus, thalamus, substantia nigra and cerebellum of aged (24-month-old) rats in comparison with adult (6-month-old) animals. In contrast, [3H]MK-801 and [3H]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, this treatment showed a significant change in both [3H]MK-801 and sodium-dependent [3H]D-aspartate binding in aged rats. These results demonstrate 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.
Araki
T
T
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Oshima
Y
Y
Kato
H
H
Shuto
K
K
Itoyama
Y
Y
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D005998:Glycine; D019331:NG-Nitroarginine Methyl Ester