A dopamine D1-like receptor-specific agonist improves the survival of septic mice

Koichi Tanaka; Mohammed E Choudhury; Satoshi Kikuchi; Ikuko Takeda; Kensuke Umakoshi; Noriyuki Miyaue; Kanta Mikami; Ayane Takenaga; Harumichi Yagi; Rintaro Shinabe; Hironori Matsumoto; Hajime Yano; Masahiro Nagai; Jun Takeba; Junya Tanaka

doi:10.1016/j.isci.2024.109587

A dopamine D1-like receptor-specific agonist improves the survival of septic mice

iScience. 2024 Mar 27;27(4):109587. doi: 10.1016/j.isci.2024.109587. eCollection 2024 Apr 19.

Authors

Koichi Tanaka^{1

2}, Mohammed E Choudhury³, Satoshi Kikuchi⁴, Ikuko Takeda^{5

6}, Kensuke Umakoshi¹, Noriyuki Miyaue⁷, Kanta Mikami³, Ayane Takenaga^{3

7}, Harumichi Yagi³, Rintaro Shinabe³, Hironori Matsumoto⁴, Hajime Yano³, Masahiro Nagai⁷, Jun Takeba², Junya Tanaka³

Affiliations

¹ Advanced Emergency and Critical Care Center, Ehime Prefectural Central Hospital, Kasugamachi, Matsuyama, Ehime 790-0024, Japan.
² Department of Aeromedical Services for Emergency and Trauma Care, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
³ Department of Molecular and Cellular Physiology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
⁴ Department of Emergency Medicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
⁵ Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
⁶ Division of Multicellular Circuit Dynamics, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan.
⁷ Department of Clinical Pharmacology and Therapeutics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.

Abstract

In this study, a murine sepsis model was developed using the cecum ligation and puncture (CLP) technique. The expression of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) in the brain increased 6 h after CLP but decreased 24 h later when elevated endogenous dopamine levels in the brain were sustained. Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride reduced dopamine levels in the striatum and increased mortality in septic mice. Dopamine D1-like receptors were significantly expressed in the brain, but not in the lungs. Intraperitoneally administered SKF-81297 (SKF), a blood-brain barrier-permeable D1-like receptor agonist, prevented CLP-induced death of septic mice with ameliorated acute lung injury and cognitive dysfunction and suppressed TNF-α and IL-1β expression. The D1-like receptor antagonist SCH-23390 abolished the anti-inflammatory effects of SKF. These data suggest that D1-like receptor-mediated signals in the brain prevent CLP-induced inflammation in both the brain and the periphery.

Keywords: Behavioral neuroscience; Biological sciences; Immunology; Natural sciences; Neuroscience; Pathophysiology; Pharmacology; Physiology.