1. A dopamine D1-like receptor-specific agonist improves the survival of septic mice
- Author
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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, and Junya Tanaka
- Subjects
Pharmacology ,Natural sciences ,Biological sciences ,Physiology ,Pathophysiology ,Neuroscience ,Science - Abstract
Summary: 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.
- Published
- 2024
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