2004 Fiscal Year Final Research Report Summary
Food allergy and immunologic disease in the intestine : the role of primary afferent neurons in the intestine
| Project/Area Number |
14570065
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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 |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY (2004)
Nara Medical University (2002-2003) |
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Principal Investigator |
KADOWAKI Makoto Institute of Natural Medicine, Division of Gastrointestinal Pathophysiology, Professor, 和漢薬研究所, 教授 (20305709)
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| Co-Investigator(Kenkyū-buntansha) |
KURAMOTO Hirofumi Kyoto Institute of Technology, Department of Applied Biology, Associate Professor, 繊維学部, 助教授 (30153373)
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| Project Period (FY) |
2002 – 2004
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| Keywords | rat intestine / food allergy / capsaicin / transient receptor potential vanilloid 1 (TRPV1) / Immunohistochemistry / calcitonin gene-related peptide (CGRP) / COX-1 / COX-2 |
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| Research Abstract |
The aim of this study was to determine the action of capsaicin in isolated rat intestine and the origin of nerve fibers expressing transient receptor potential vanilloid 1 (TRPV1 : capsaicin receptor) in the rat jejunum by combination of functional and immunohistochemical experiments. Capsaicin (1μM) produced a prolonged relaxation response (52.8±15.3% of the relaxation response to papaverine, mean ± S.D., n=27) of the isolated jejunum in the presence of atropine and guanethidine. Pretreatment with the TRPV1 antagonist, capsazepine (10μM) and ruthenium red (3μM) significantly reduced the relaxation response to capsaicin by 78% (P<0.01) and 38% (P<0.05), respectively. Tetrodotoxin and calcitonin gene-related peptide (CGRP)-desensitization significantly reduced the response to capsaicin by 72% (P<0.01) and 42% (P<0.01), respectively. Therefore, we investigated the distribution of TRPV1-immunoreactivity (IR) in the myenteric plexus of the rat jejunum. Using antisera raised against either the N-terminal or C-terminal domains of rat TRPV1, TRPV1-IR was present in the nerve fibers, but not in the cell bodies of myenteric neurons. These TRPV1-immunoreactive nerve fibers were running in myenteric ganglia and their interconnecting strands. Most TRPV1-immunoreactive nerve fibers showed CGRP-IR, whereas few VR1-immunoreactive nerve fibers showed substance P-IR. After chronic denervation of the extrinsic nerve supply to the jejunum, both the relaxation response to capsaicin and TRPV1-immunoreactive nerve fibers completely disappeared. These findings indicate that these TRPV1-immunoreactive nerve fibers in the rat jejunum derive from extrinsic neurons and that activation of TRPV1 produces the relaxation response in the rat jejunum, at least in part, through the release of CGRP from nerve fibers expressing TRPV1.
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