2021 Fiscal Year Final Research Report

Is the angiotensin II-induced persistent activity in the subrfornical neurons physiological or pathological?

Research Project

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Project/Area Number	19K06403
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 42020:Veterinary medical science-related
Research Institution	Tottori University
Principal Investigator	SHIBUYA Izumi 鳥取大学, 農学部, 教授 (50162649)
Co-Investigator(Kenkyū-buntansha)	保坂善真鳥取大学, 農学部, 教授 (00337023) 樋口雅司鳥取大学, 農学部, 准教授 (70614791) 北村直樹鳥取大学, 農学部, 准教授 (80301951)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	脳弓下器官 / アンジオテンシンII / GABA / Galanin / ANP
Outline of Final Research Achievements	The subfornical organ (SFO) is senses circulating angiotensin II (AII) because of its lack of the blood-brain barrier (BBB), and therefore, regarded as the major site of the central nervous system controlling the volume and osmolality of the body fluid. In the present study, we measured the cytosolic Ca2+ concentration ([Ca2+]i) and the membrane current in acutely isolated SFO neurons. We found that only AII given at nanomolar concentrations induced persistent increases of [Ca2+]i and that the [Ca2+]i increase was reversibly suppressed by the physiological inhibitory ligands in the SFO, GABA, galanin and ANP. These results suggest that the AII-induced persistent [Ca2+]i increase is the physiological regulatory mechanism for SFO neurons, and does not reflect pathological reactions.
Free Research Field	神経生理学
Academic Significance and Societal Importance of the Research Achievements	人の体重の60％以上は水であるが、その大量の液体の量と、その浸透圧はわずか数％の範囲で調節されている。血圧・体液量・体液浸透圧は神経性、および液性に調節される。液性調節の中で主要なホルモンであるアンジオテンシンIIは、血液脳関門を欠く脳弓下器官（SFO)のニューロンによって直接感知される。今回の研究では、アンジオテンシンIIがSFOニューロンの細胞内Ca2+濃度を持続的に上昇させること、およびこの現象が飲水行動や抗利尿反応の発現に重要な生理的反応であると示唆する結果を得た。この成果は今後、体液量・浸透圧に関する疾患の予防・治療に役立つと思われる。