The functional analysis of L-DOPA neurotransmission in the nucleus tractus solitarii

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K14923
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Yokohama City University
• Principal Investigator: Masukawa Daiki 横浜市立大学, 医学部, 助教 (10711898)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: L-DOPA / GPR143 / Neurotransmitter / NTS / Aortic depressor nerve

Outline of Final Research Achievements

We have proposed that L-DOPA is a neurotransmitter in the primary baroreceptor afferents terminating in the nucleus tractus solitarii (NTS). We investigated whether depressor and bradycardic responses to L-DOPA was mimicked by stimulating aortic depressor nerve (ADN) using optogenetic procedure in rats. We injected adeno-associated virus encoding ChR2-EYFP or EYFP into the ganglion of ADN. Four to five weeks after injection, ChR2-EYFP and EYFP signals were partially localized with tyrosine hydroxylase-positive neurons in the NTS of the brain tissues. Photostimulation (473 nm, 40 mW, 20 Hz, 20s) from the surface of the NTS induces depressor, bradycardic response in the animals expressing ChR2-EYFP, but not EYFP in the ADN. The effects of photostimulation were attenuated by treatment with L-DOPA cyclohexylester, an antagonist for L-DOPA, in the NTS, as were those of exogenously applied L-DOPA. These results suggested that L-DOPA is a neurotransmitter in the NTS.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果より、ドーパが大動脈神経から NTS に終末する神経において、生理的に血圧を調節する可能性が示唆された。この結果はドーパが NTS における神経伝達物質であることを示唆する。従来、ドーパミンの前駆体に過ぎず、それ自体に活性がないと考えられてきたドーパが神経伝達物質として機能することを証明することは、薬理学の教科書を塗り替える可能性を秘めている。この点が本成果の学術的意義である。