| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
It had been demonstrated that, in the canine small intestine in vivo, polarized enteric reflexes that cause a contraction on the oral side of the stimulus and a relaxation on the anal side (an ascending contraction and a descending relaxation in the peristaltic reflex) were initiated by mechanical or chemical stimulation of the mucosa. Recently, we have found that 5-HT3 receptors play an important role in the peristaltic reflex in the canine jejunum. In the present study, we investigated the involvement of nitric oxide in the peristaltic reflex mediated by 5-HT3 receptors in dogs anesthetized with urethane and alpha-chloralose. A neurally decentralized jejunal loop was partitioned into two segments with respect to blood supply. Drugs were infused intra-arterially into each segment and mechanical responses in the oral and anal segments were monitored.
Each ascending contraction induced by administration of 2-methyl-serotonin (an agonist of 5-HT3 receptors), 5-methoxytryptamine (an agonis
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t of 5-HT4 receptors), and acetylcholine to the anal segment, and by stroking the mucosa in the anal segment was augmented by treating the oral or anal segment with NG-nitro-L-arginine (L-NNA, an inhibitor of nitric oxide synthase). Effects of these augmentation were restored by L-arginine but not D-arginine. The descending relaxations induced by administration of 2-methyl-serotonin to the oral segment and by stroking the mucosa in the oral segment were reduced by treating the anal segment with L-NNA.The inhibitory effects of L-NNA was restored by L-arginine. L-NNA did not affect the spontaneous contractions.
These results suggest firstly that nitric oxide is released from the enteric neurons when peristaltic reflexes are activated, secondly that nitoric oxide plays a role as a transmitter of final neurons in the reflex pathway for the descending relaxation, and finally that nitric oxide partially inhibits a cholinergic transmission in the ascending pathway activated by chemical and mechanical stimulation, thus nitric oxide regulates the magnitude of the ascending contraction. Less
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