| Project/Area Number |
14560252
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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 |
Basic veterinary science/Basic zootechnical science
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| Research Institution | Osaka Prefecture University |
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Principal Investigator |
HATA Fumiaki Osaka Prefecture University, Graduate School of Agriculture and Life Sciences, Professor, 農学生命科学研究科, 教授 (60028363)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | gastrointestinal motility / inhibitory neurotransmission / development and aging / PACAP / PHI / nitric oxide / smooth muscle relaxation / descending relaxation / 下行性弛緩 |
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| Research Abstract |
We have reported that the role of nitric oxide as an inhibitory neurotransmitter in the gastrointestinal tract decreased with development and aging of rats. On the contrary, vasoactive intestinal peptide, which is one of peptide neurotransmitters, has a role as an inhibitory neurotransmitter in the distal colon of the rat and increased its role with development and aging of the rat. In the present study, the role of pituitary adenylate cyclase activating peptide (PACAP) which is another peptide neurotransmitter was examined. Major findings are as follows.
1.Electrical field stimulation (EFS)-induced neurogenic relaxant response was largest in 2-week-old rats and decreased with age.
2.In 2-week-old rats, there are two neuronal pathways for the relaxation. One is cyclic AMP-PKA pathway and the other is tyrosine kinase-SK channel pathway. The former has a dominant role.
3.In 8-week--old rats, the role of the cyclic AMP-PKA pathway significantly decreases and the role of tyrosine kinase-SK ch
… More
annel pathway becomes to have a major role.
Since action of PACAP was associated with SK channels, we next examined the localization of SK channels in the gastrointestinal tract by immuno-histological methods. SK channels were localized in the interstitial cells instead of smooth muscle cells. These cells were stained with anti-proryl 4-hydroxyalase antibody but not anti-c-kit antibody. Thus, these cells were identified as fibroblast like cells. From these findings, it seems that PACAP acts fibroblast like cells and induces hyperpolarization via opening of SK channels. The hyperpolarization is conducted to smooth muscle cells though gap junctions and in turn results in relaxation of smooth muscle cells.
We also examined the inhibitory mediators in the fundus of mice and obtained the following results.
1.EFS-induced neurogenic relaxation consists of a rapid transient relaxation and delayed long lasting relaxation.
2.It was suggested that the transient relaxation is mediated by nitric oxide and the delayed relaxation is mediated by PACAP and the peptide histidine isoleucine (PHI)
3.Both peptides tonically regulate the resting tone of the fundus.
4.It was also suggested that PACAP which was believed as an antagonist of the PACAP receptor, blocks the PHI receptor. Less
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