Effects of vinconate on age-related alterations in [3H]MK-801, [3H]glycine, sodium-dependent D-[3H]aspartate, [3H]FK-506 and [3H]PN200-110 binding in rats.
We investigated the effects of age and (+/-)-methyl-3-ethyl-2,3,3a,4-tetrahydro-1 H-in-dolo[3,2,1-de] [1,5] naphthyridine-6-carboxylate hydrochloride (vinconate), an indolonaphthyridine derivative, on calcium channels, neurotransmitter receptor systems and immunophilin in Fischer rat brain using quantitative receptor autoradiography. [3H]MK-801, [3H]glycine, sodium-dependent D-[3H]aspartate, [3H]FK-506 and [3H]PN200-110 were used to label N-methyl-D-aspartate (NMDA) receptors, glycine receptors, excitatory amino acid transport sites, FK-506 binding proteins (FKBP) and voltage-dependent L-type calcium channels, respectively. [3H]Glycine and sodium-dependent D-[3H]aspartate binding significantly decreased in the frontal cortex, parietal cortex, striatum, nucleus accumbens, hippocampus, thalamus, substantia nigra and cerebellum of 24 month old rats in comparison with 6 month old animals. In contrast, [3H]MK-801, [3H]FK-506 and [3H]PN200-110 binding showed no significant changes in the brain of 24 month old rats. Intraperitoneal chronic treatment with vinconate (10 and 30 mg/kg, once a day for 4 weeks) dose-dependently ameliorated the significant reduction in [3H]glycine and sodium-dependent D-[3H]aspartate binding in the brain of 24 month old rats. These results demonstrate that glycine receptors and excitatory amino acid transport sites are more susceptible to aging processes than NMDA receptors, immunophilin and voltage-dependent L-type calcium channels. Furthermore, our findings suggest that vinconate may have a beneficial effect on age-related changes in glycine receptors and excitatory amino acid transport sites.
Araki
T
T
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Kato
H
H
Nagaki
S
S
Shuto
K
K
Fujiwara
T
T
Itoyama
Y
Y
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D017275:Isradipine / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D018009:Receptors, Glycine / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D016559:Tacrolimus / Q000378:metabolism; D022021:Tacrolimus Binding Proteins; D014018:Tissue Distribution; D014748:Vinca Alkaloids / Q000494:pharmacology*
D015220:Calcium Channels; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018691:Excitatory Amino Acid Antagonists; D006360:Heat-Shock Proteins; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D014748:Vinca Alkaloids; D001224:Aspartic Acid; D016291:Dizocilpine Maleate; C038627:vinconate; D012964:Sodium; D022021:Tacrolimus Binding Proteins; D005998:Glycine; D016559:Tacrolimus; D017275:Isradipine