Project/Area Number |
07670011
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General anatomy (including Histology/Embryology)
|
Research Institution | Shiga University of Medical Science |
Principal Investigator |
FUJIMIYA Mineko Shiga Univ.Med.Sci./Associat Professor, 医学部, 助教授 (10199359)
|
Co-Investigator(Kenkyū-buntansha) |
OKUMIYA Kiyohito Kochi.Med.Coll./Research Associate, 医学部, 助手 (20253346)
TOKUNAGA Yoshimitsu Shiga Univ.Med.Sci./Research Associate, 医学部, 助手 (90263037)
|
Project Period (FY) |
1995 – 1997
|
Project Status |
Completed (Fiscal Year 1997)
|
Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
Keywords | Gastrointestinal / Serotonin / Serotonin Receptor / Motility / Luminal release / Immunoelectron microscopy / クロモグラニンA / 腸管 / EC細胞 |
Research Abstract |
The functional role of serotonin (5HT)-containing enterochromaffin cells in the gastrointestinal tract has been studied. First of all, we examined the mechanism to regulate the release of 5HT from isolated perfused rat duodenum. Cholinergic muscarinic mechanism stimulated the release of 5HT into the intestinal lumen. CCK stimulated the release of 5HT into the lumen, this mechanism was mediated by the cholinergic mechanism. VIP and PACAP inhibited the release of 5HT into the lumen via the VIP-2 receptors on the EC cells. VIP/PACAPs and NO were strongly related on the inhibition of 5HT release. To examine the functional role of 5HT released from the EC cells, the effect of 5HT receptor antagonists on the intestinal motility was investigated. 5HT-3 receptor antagonist strongly blocked the duodenal motility. 5HT-4 receptor antagonist weekly blocked, however 5HT-1 or-2 receptor antagonist did not change the motility. Finally, we examined the change in the intracellular localization of 5HT after stimulation of luminal release of 5HT by immunoelectron microscopy. Since we obtained the evidence that the luminal release of 5HT was stimulated by the high intraluminal pressure, the isolated perfused duodenum was exposed to the high luminal pressure, fixed and prepared for immunoelectron microscopic study. Immunogold particles which react to 5HT were concentrated over the secretory granules in normal conditions, however they diffusely scattered over the extragranular cytoplasm and over the microvilli in the stimulated duodenum. These results suggest that 5HT might be diffusely released from the EC cells to the intestinal lumen by a diacrine manner of secretion.
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