Screening and profiling of GPCRs in vagal afferent nerve
| Project/Area Number |
18K14845
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 46030:Function of nervous system-related
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| Research Institution | Tohoku University |
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Principal Investigator |
Kano Kuniyuki 東北大学, 薬学研究科, 助教 (50636404)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 求心性迷走神経 / 生理活性脂質 / Gタンパク質共役型受容体 / 迷走神経 / GPCR |
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| Outline of Final Research Achievements |
For a comprehensive analysis of gene expression in vagal afferents, we performed RNA sequencing on vagal afferents (nodose ganglia). Many GPCRs for bioactive lipids including LPA, S1P, LysoPS, prostanoid and leukotriene. In situ hybridization analysis revealed that S1P3 was highly expressed in most neurons. In contrast, LPA3, LPA5, LPS3 and CysLT2 were detected in small groups. To know whether these lipid receptors activate vagal afferents, we examined the expression of c-fos, a marker for neuronal activity, in the medulla oblongata. The administration of each GPCR agonist increased c-fos mRNA level, suggesting that afferent vagal nerve is excited by these GPCRs activation. We also found some novel pharmacological actions of each GPCR agonist in vagal afferents-dependent manner. Overall, this study provides a novel lipid receptor-dependent sensing mechanisms in vagal afferents. These receptor agonists have promise as drugs for regulating vagal activity.
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| Academic Significance and Societal Importance of the Research Achievements |
迷走神経はほぼ全ての内臓機能を支配する神経であり、この神経の活性化によって臓器機能が変化する。最近、迷走神経を標的とした疾患治療戦略が注目されているが、迷走神経の活性化機構の理解が十分ではないことから、電気刺激デバイスを外科的に埋め込むことで迷走神経を活性化させる必要がある。本研究では迷走神経の新たな活性化機構を明らかにすべく、特に脂質を認識する受容体に着目して解析したところ、実際に脂質受容体の作動薬が迷走神経を活性化させ、一部の臓器機能を変化させることを見出した。従って、今後これらのメカニズムをより詳細に解析することで、脂質受容体を通じた迷走神経制御が可能になることが期待される。
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Report
(3 results)
Research Products
(6 results)
