The function of mast cell-derived mediators in visceral hypersensitivity
| Project/Area Number |
17K09037
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pain science
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| Research Institution | Osaka Prefecture University |
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Principal Investigator |
Miyai Kazumasa 大阪府立大学, 総合リハビリテーション学研究科, 教授 (60283933)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 内臓感覚 / 膀胱 / 直腸 / ヒスタミン受容体 / アデノシン三リン酸 / グルコース / ヒスタミン / ATP / 肥満細胞 / 管腔臓器 |
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| Outline of Final Research Achievements |
The mucosal epithelium of urinary bladder or rectum secretes ATP in response to mechanical/chemical stimulation, and transmits the visceral sensation to the central nervous system. We focused on the histamine receptor (H1-4) signaling pathways and examined their effects on ATP release from their epithelium.
Urinary bladder epithelium (urothelium) specifically expressed H3 mRNA, whereas H1 mRNA was expressed in rectal epithelium. Histamine had different effects on ATP release under unstimulated condition depending on its concentration. On the other hand, under physiologically stimulated condition, ATP release from rectal epithelium was facilitated by low concentration of histamine and suppressed by H1 inhibitor, whereas low concentration of histamine and H3/4 antagonist inhibited urothelial ATP release. Moreover, pretreatment of histamine enhanced ATP release from urothelium in response to stimulation of Escherichia coli-derived lipopolysaccharide.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、内臓知覚過敏を伴う疾患群（過活動膀胱や過敏性腸症候群）は増加傾向にあるが、現在のところ、これらの疾患に対する薬物的な治療は内臓運動の抑制を標的にしたものばかりであり、内臓感覚そのものに着目した創薬の推進には重要な意義がある。本研究により、ヒスタミン受容体シグナル経路が膀胱や直腸の内臓感覚を調節している可能性が示唆された。外来性ヒスタミンの作用機序は複雑で更なる解析を必要とするが、膀胱・直腸ともに上皮に特異的に発現しているヒスタミン受容体の阻害薬はATP分泌を抑制する傾向が認められたことから、これら阻害薬は内臓知覚過敏に対する治療薬となる可能性がある。
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Report
(4 results)
Research Products
(2 results)
