Effect of nitric oxide synthase inhibitor on age-related changes in second messenger systems and calcium channels in rats.
We investigated the effects of age and nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on protein kinase C (PKC), adenylyl cyclase, calcium/calmodulin-independent cyclic-AMP phosphodiesterase (cyclic-AMP PDE) and voltage-dependent L-type calcium channels in Fischer rat brain using autoradiography. [3H]Phorbol 12,13-dibutyrate (PDBu), [3H]forskolin, [3H]rolipram and [3H]PN200-110 were used to label PKC, adenylyl cyclase, cyclic-AMP PDE and calcium channels, respectively. [3H]Forskolin binding significantly decreased in the striatum, hippocampal CA3 sector, dentate gyrus, hilus, thalamus, substantia nigra and cerebellum of 24-month-old (aged) rats, as compared with 6-month-old (adult) animals. [3H]Rolipram binding also showed an age-related reduction in the thalamus and cerebellum in rats. In contrast, no age-related changes were observed in [3H]PDBu and [3H]PN200-110 binding in the rat brain. Chronic treatment with L-NAME (5 mg/kg, once a day for 4 weeks) showed no significant changes in [3H]PDBu, [3H]rolipram and [3H]PN200-110 binding in aged rat brains. However, this treatment significantly increased age-related decreases in [3H]forskolin binding in the frontal cortex; striatum and hippocampal CA1 sector in rats. The results demonstrate that [3H]forskolin binding in the rat brain is more susceptible to aging processes than [3H]PDBu, [3H]rolipram and [3H]PN200-110 binding. Furthermore, our study shows that chronic treatment with NO inhibitor increases the age associated changes in [3H]forskolin binding in most brain areas of aged rats. These findings suggest that NO may play a key role in the regulation of adenylyl cyclase system during aging processes.
Araki
T
T
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Kato
H
H
Shuto
K
K
Fujiwara
T
T
Itoyama
Y
Y
D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000033:anatomy & histology; D001923:Brain Chemistry / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D011916:Rats, Inbred F344; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019331:NG-Nitroarginine Methyl Ester