| Project/Area Number |
09671237
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | NAGASAKI UNIVERSITY |
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Principal Investigator |
KANEMATSU Takashi (1998) School of Medicine, Nagasaki University, Professor, 医学部, 教授 (40128004)
大野 康治 (1997) 長崎大学, 医学部附属病院, 助手 (70274644)
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| Co-Investigator(Kenkyū-buntansha) |
SHIGEMATSU Kazuto School of Medicine, Nagasaki University, Associate Professor, 医学部, 助教授 (20154205)
TANIYAMA Kohtaro School of Medicine, Nagasaki University, Professor, 医学部, 教授 (70030898)
NIWA Masami School of Medicine, Nagasaki University, Professor, 医学部, 教授 (20136641)
兼松 隆之 長崎大学, 医学部, 教授 (40128004)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Hischsprung's disease / neurotransmitters / endothelin receptors / substance P receptors / myenteric plexus / ileus / quantitative receptor imaging system / ヒルシュスプルング病 |
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| Research Abstract |
We examined the changes in receptors of neurotransmitters such as endothelin (EL) and substance P in the intestinal wall related to the dysfunction of large-intestinal motility in Hirselisprung disease and its animal model of congenital aganglionosis (AR) rat, the rat with a mutant endothelin ET_B receptor. We used our newly-developed method for analyzing the receptor dynamics ; the quantitative receptor-imaging system with three experimental techniques, 1) in vitro radioligand-binding technique for functional sites of receptors, 2) quantilative radioimnunohistochernical technique for sites of receptor proteins maturation, and 3) in situ hybridization technique for production sites of receptors with 35S-cRNA probes. We found the existence of ET_B receptors in the main principal cell (cholinergic neuronal cell body) in Auerbach's plexus, and small enteroglia in the colon of patients and AR rats. With the use of our methods, we confirmed the finding that ^1^2^5IRL162O, a selective radioligand for the ET_B receptor, merely bound to the section of colon with Aucrbach's plexus isolated from a patient with Hirschsprung's disease. In this case of patient, we failed to detect a compensatory increase of substance P receptor, using our method. Interestingly, in another patient with Hirschsprung's disease no abnormal binding of ^1^2^5I-1RL1620 was observed, however, a very lower amount of the expression of substance P receptor in Anerbach's plexus. Thus, we confirmed the pathopliysiological significance of the ETB receptor in the onset of Hirschsprung disease, and the possible another gene-defect in this disease. A factor regulating substance P receptor function may shed some light on the discovery of the heterogeneity of Hirschsprung's disease.
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