| Project/Area Number |
18580297
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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 |
TAKEUCHI Tadayoshi Osaka Prefecture University, Graduate School of Life and Environmental Sciences, Professor (00171611)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Pharmacology / Gastrointestinal motility / Myentric plexus / Muscarinic receptor / SK channels / Nicotinic receptors / Mechanisms for Ca^<2+>sensitization / Inhibitory neurotransmission / Ca感受性増強機構 / アセチルコリン遊離 / Alendronate |
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| Research Abstract |
Since there are still a lot of uncertain points for the regulating mechanism, of peristaltic movement that is important in the transit of the intestinal contents, we conducted the studies about interaction among modulators of intestinal movements. In the present studies, the results were obtained as follows.
1. It was demonstrated that the M_3 receptor plays a major role in ACh-mediated phasic contraction in the ileum. By contrast, the M_2 receptor has not only a partial role in phasic contraction, but also is involved in sustained contraction, probably by negatively modulating the release of SP.
2. It was demonstrated that orexin is involved in the ascending and descending pathways of the peristalsis in the mouse jejunum. In the ascending pathways, orexin neuron constitutes the same pathway as cholinergic neuron and is present upstream of cholinergic interneuron. In contrast, orexin and cholinergic neurons function separately in the descending pathways. To our knowledge, this is the first report to suggest a role of orexin A as a mediator of interneuron in the gastrointestinal tract.
3. It was described that alendronate decreases the tone of lower esophageal sphincter by inhibiting cholinergic nervous activity and for the first times the underlying mechanisms involved in the esophageal damage caused by alendronate administration.
4. It was shown the first evidence that Ca^<2+>sensitization has a minor role in the sustained contraction induced by activation of muscarinic receptors in the circular muscle of the rat distal colon, with the result that the amplitude of the sustained contraction is very low.
5. SK channels, most likely the SK2 subunit, was found to be involved in the regulation of the ACh_release by modulating the nAChR excitation of guinea pig cholinergic neurons. The results suggested a functional interaction between SK2 channels and nAChRs.
A part of the mechanisms for regulating the peristaltic movement was manifested from these studies.
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