| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
Background : C-kit receptor is known to play an important role in the development of interstitial cells of Cajal (ICC) which are the pacemaker cells in the gastrointestinal tract. Clinically Hirschsprung's disease, infantile hypertrophic pyloric stenosis and chronic idiopathic intestinal pseudo-obstruction have abnormalities in the development of ICC. The c-kitis a receptor tyrosine kinase and is encoded by Ws locus. Ws/Ws rats are mutant animals which have a 12-base deletion in tyrosine kinase domain of c-kit gene. Aim : To investigate the characteristics of gastric motility of Ws/Ws rats including nitrergic neuron with electrical field stimulations (EPS). Method : Muscle strips from mid-body of the stomach were dissected along the circular axis from male Ws/Ws rats and controls. The strips were suspended in organ baths filled with Krebs-Henseleit buffer. The strips were stimulated by transmural electrical field stimulations (EPS, 400 mA, 1 msec, 1-10 Hz, for 30 sec). When measuring r
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elaxations, the strips were precontracted with 5-hydroxytryptamine. In the experiments of non-cholinergic (NANC) relaxations, the strips were pretreated with atropine and guanethidine. NG-nitro-L-arginine methyl ester (L-NAME) was used as a NO synthase inhibitor and sodium nitroprusside (SNP) as a NO donor. Hisitologically cGRP, substanceP, VIP, nNOS and Ach neurons were also studied. Result : EPS-evoked muscle contractions and relaxations were significantly enhanced in Ws/Ws rats than control rats. EPS-evoked NANC relaxations were tend to be enhanced in Ws/Ws rats compared with control rats. L-NAME inhibited EPS-evoked NANC relaxations and the suppression rate of L-NAME was significantly lower in Ws/Ws rats than control rats. SNP inhibited NANC relaxations in a dose-response manner and the effect of SNP was attenuated significantly in Ws/Ws rats compared with control rats. There were no significant difference in distribution of CGRP, substance P and VIP neurons between Ws/Ws rats and controls. NOS-positive neurons were more dense in WVPfls rats than controls. Conclusions : In the diseases based on c-kit abnormality, cooperative peristalsis of the GI tract does not occur, however, contractions and relaxations in response to neurogenic stimulations were enhanced. Histologically, NOS activity were enhanced, however, nitergic neurotransmission was disturbed. Less
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