Galpha14-mediated NK1 receptor cell signaling in the celiac-superior mesenteric ganglion

Research Project

Project/Area Number	16K15671
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Anesthesiology
Research Institution	Tohoku University
Principal Investigator	Yamauchi Masanori 東北大学, 医学系研究科, 教授 (00404723)
Co-Investigator(Kenkyū-buntansha)	杉野繁一東北大学, 大学病院, 助教 (00423765)
Research Collaborator	RUIZ-VELASCO Victor IMAMURA Yuka ENDO Yasuhiro MURAKAMI Toru
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000) Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords	腹腔神経叢 / サブスタンスP / Gタンパク共役受容体 / 内臓痛 / パッチクランプ / タキキニン / シングルセル解析 / パッチクランプ記録 / 外科 / シグナル伝達 / がん
Outline of Final Research Achievements	Celiac-superior mesenteric ganglion (CSMG) is involved in regulating abdominal organ function, and is also involved in visceral pain transmission. We investigated the modulation of Ca2+ and M-type K+ currents by the tachykinin substance P (SP)/neurokinin-1 receptor signaling pathway in acutely dissociated rat CSMG neurons (with Prof. Ruiz-Velasco at Penn State University). The results of an electrophysiological study showed that SP blocked the Ca2+ and M-currents. Silencing the Gα14 subunit, a member of the Gαq/11 subfamily, significantly attenuated the Ca2+ and M-current blocks. The results suggest that in CSMG neurons, SP-stimulated NK-1 receptors modulate Ca2+ and M-currents by employing a single pathway requiring Gα14 subunits. Moreover, to identify genetic mechanisms in the pathway, we have developed a single-cell whole transcriptome sequencing method using a neuron after electrophysiological recording. We will find changes in the transcriptome of the neurons in near future.
Academic Significance and Societal Importance of the Research Achievements	Gα14は腹腔神経節ニューロンに特異的に発現，機能しているシグナル分子であることを突き止めたので，腹腔神経節だけに作用する分子標的薬が開発できるかもしれない．たとえば腹部手術ならその分子標的薬と腹横筋膜面(TAP)ブロックを併用することで，麻薬の必要量が減少し，質の高い麻酔管理ができるであろう．またがん患者では麻薬投与量を大幅に減量して，さらに副作用の少ない腹腔神経叢ブロックを提供できるかもしれない．