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

2018 Fiscal Year Final Research Report

• 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
• 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

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.

Free Research Field

麻酔科学

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．