Elucidation of the basis for transmission of the cholecystokinin receptor CCK1R in the brain-gut correlation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06746
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Hokkaido University
• Principal Investigator: konno kohtarou 北海道大学, 医学研究院, 助教 (20599641)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: コレシストキニン / CCK / 脳腸相関

Outline of Final Research Achievements

Gut hormone cholecystokinin (CCK) mediates postprandial reduction of food intake by acting on CCK1 receptors (CCK1R) on vagal afferents. The present study examined CCK1R expression in the dorsal vagal complex (DVC) in the mouse brain. Specific immunohistochemical labeling for CCK1R was intense in the central branch of vagal afferents terminating in the nucleus tractus solitarius (NTS) and area postrema (AP). Moreover, CCK1R-immunoreactive elements in the NTS and AP were overlapped with diffusing areas of Evans Blue dye administered into the circulation. These results suggest the possibility of activation of CCK1R in the DVC by hormonal CCK diffusing from the AP lacking the blood-brain barrier.

Free Research Field

神経解剖学

Academic Significance and Societal Importance of the Research Achievements

現在に至るまで「消化管で産生放出されたCCKが、どのようにして脳に作用するか」という基本的情報は大きく欠落していた。CCK1Rの詳細な局在解析により、CCK1Rは延髄の迷走神経背側複合体に局在することが明らかとなった。さらに、血液脳関門を欠く最後野から拡散するホルモン性CCKによってDVCのCCK1Rを活性化する可能性が示唆されることから、CCKが関与する脳腸機能相関の情報伝達基盤の解明に大きく寄与する研究成果である。