INFLUENCE OF AGE ON THE SIGNAL-TRANSDUCTION PATHWAY OF NONADRENERGIC NONCHOLINERGIC NEUROTRANSMITTERS IN THE RAT GASTRIC FUNDUS

1 The influence of aging on the relaxant response and the change in cy clic nucleotide content induced by vasoactive intestinal polypeptide ( VIP), nitric oxide (NO), electrical field stimulation of the nonadrene rgic non-cholinergic neurones and substances acting at different level s of the cyclic AMP and cyclic GMP transduction pathways was studied i n longitudinal muscle strips of the rat gastric fundus. 2 The relaxant responses to VIP, sustained electrical stimulation, forskolin and 3-i sobutyl-1-methylxanthine were reduced with age, while the responses to dibutyryl cyclic AMP were not. The increase in cyclic AMP content ind uced by sustained electrical stimulation and forskolin was lower in ol d rats. 3 The relaxant responses to NO and to short train electrical s timulation were similar in the three age groups. The inhibitory effect of N-G-nitro-L-arginine methyl ester on relaxations induced by short train electrical stimulation was more pronounced in old rats. The rela xant responses to sodium nitroprusside (SNP), 8-bromo-cyclic GMP and z aprinast were reduced with age. SNP induced a similar elevation of the cyclic GMP content in the three age groups. 4 These results suggest t hat aging differentially affects the cyclic AMP and cyclic GMP pathway for relaxation by VIP and NO in the rat gastric fundus, as the defect seems to occur at the level of the adenylate cyclase and cyclic GMP-d ependent protein kinase respectively.