EFFECT OF NITRIC-OXIDE SYNTHASE INHIBITOR ON AGE-RELATED-CHANGES IN 2ND MESSENGER SYSTEMS AND CALCIUM CHANNELS IN RATS

We investigated the effects of age and nitric oxide synthase inhibitor , N-G-nitro-L-arginine methyl ester (L-NAME), on protein kinase C (PKC ), adenylyl cyclase, calcium/calmodulin-independent cyclic-AMP phospho diesterase (cyclic-AMP PDE) and voltage-dependent L-type calcium chann els in Fischer rat brain using autoradiography. [H-3]Phorbol 12,13-dib utyrate (PDBu), [H-3]forskolin, [H-3]rolipram and [H-3]PN200-110 were used to label PKC, adenylyl cyclase, cyclic-AMP PDE and calcium channe ls, respectively. [H-3]Forskolin binding significantly decreased in th e striatum, hippocampal CA3 sector, dentate gyrus, hilus, thalamus, su bstantia nigra and cerebellum of 24-month-old (aged) rats, as compared with 6-month-old (adult) animals. [H-3]Rolipram binding also showed a n age-related reduction in the thalamus and cerebellum in rats. In con trast, no age-related changes were observed in [H-3]PDBu and [H-3]PN20 0-110 binding in the rat brain. Chronic treatment with L-NAME (5 mg/kg , once a day for 4 weeks) showed no significant changes in [H-3]PDBu, [H-3]rolipram and [H-3]PN200-110 binding in aged rat brains. However, this treatment significantly increased age-related decreases in [H-3]f orskolin binding in the frontal cortex, striatum and hippocampal CAI s ector in rats. The results demonstrate that [H-3]forskolin biding in t he rat brain is more susceptible to aging processes than [H-3]PDBu, [H -3]rolipram and [H-3]PN200-110 binding. Furthermore, our study shows t hat chronic treatment with NO inhibitor increases the age associated c hanges in [H-3]forskolin binding in most brain areas of aged rats. The se findings suggest that NO may play a key role in the regulation of a denylyl cyclase system during aging processes.