2001 Fiscal Year Final Research Report Summary
Intestinal motility immune systems in Hirschsprung's disease model animals
| Project/Area Number |
12460132
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
OZAKI Hiroshi Graduate school of Agriculture and Life Sciences, Veterinary Pharmacology, The University of Tokyo, Assoc. Prof., 大学院・農学生命科学研究科, 助教授 (30134505)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAYAMA Hiroyuki Graduate school of Agriculture and Life Sciences, Veterinary Pathology, The University of Tokyo, Assoc. Prof., 大学院・農学生命科学研究科, 助教授 (40155891)
HORI Masatoshi Graduate school of Agriculture and Life Sciences, Veterinary Pharmacology, The University of Tokyo, Assist. Prof., 大学院・農学生命科学研究科, 助手 (70211547)
SATO Koichi Graduate school of Agriculture and Life Sciences, Veterinary Pharmacology, The University of Tokyo, Assist. Prof., 大学院・農学生命科学研究科, 助手 (90205914)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Hirschsprung's disease / motility / contraction / morphology / endothelin B receptor / smooth muscle / megaileum / NO |
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| Research Abstract |
The endothelin ETB receptor null rat (ETB(-/-)R) has an intestinal segment without ganglia, and this rat is characterized by an intestinal obstruction similar to those observed in human Hirschsprung' s disease. In the present study, we have examined the myogenic mechanism responsible for the obstruction in the ETB(-/-)R.
The ETB(-/-)R has an enlarged belly and the average life span was 18.1 day. The bowel from the rectum to the lower part of the small ileum, was constricted whereas the upper region was dilated with fecal stasis and thus presented megaileum. The constricted muscle segments without ganglia had a greater increase in absolute force when stimulated by carbachol, high K+, and endothelin-1 comparing to that of normal siblings. In contrast, in the dilated part with ganglia, the absolute contractile force due to these stimulants in the ETB(-/-)R was not different from that in the ETB(+/+)R. Such a functional hypertrophy of the musculature was observed in the parts of the colon, caecum, and distal ileum without ganglia, but not in the part of the proximal ileum and jejunum with ganglia. Morphological study demonstrated that the thickness of the circular and longitudinal muscle layers was greater in the constricted part of the intestine in the ETB(-/-)R, and these changes were associated with an increase in the number of smooth muscle cells.
The above findings suggest that both the increased contractility of smooth muscle and the increased thickness of the intestinal muscular wall may contribute to the intestinal obstruction in the ETB(-/-)R.
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