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  2. Dopamine regulates astrocytic IL-6 expression and process formation via dopamine receptors and adrenoceptors

Dopamine regulates astrocytic IL-6 expression and process formation via dopamine receptors and adrenoceptors

  • Eur J Pharmacol. 2022 Aug 5;928:175110. doi: 10.1016/j.ejphar.2022.175110.
Kohei Morimoto 1 Mai Ouchi 1 Taisuke Kitano 1 Ryota Eguchi 1 Ken-Ichi Otsuguro 2
Affiliations

Affiliations

  • 1 Laboratory of Pharmacology, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
  • 2 Laboratory of Pharmacology, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan. Electronic address: otsuguro@vetmed.hokudai.ac.jp.
Abstract

Dopamine levels in the central nervous system change under pathological conditions such as Parkinson's disease, Huntington's disease, and addiction. Under those pathological conditions, astrocytes become reactive astrocytes characterized by morphological changes and the release of inflammatory cytokines involved in pathogenesis. However, it remains unclear whether dopamine regulates astrocytic morphology and functions. Elucidating these issues will help us to understand the pathogenesis of neurodegenerative diseases caused by abnormal dopamine signaling. In this study, we investigated the effects of dopamine on IL-6 expression and process formation in rat primary cultured astrocytes and acute hippocampal slices. Dopamine increased IL-6 expression in a concentration-dependent manner, and this was accompanied by CREB phosphorylation. The effects of a low dopamine concentration (1 μM) were inhibited by a D1-like receptor antagonist, whereas the effects of a high dopamine concentration (100 μM) were inhibited by a β-antagonist and enhanced by a D2-like receptor antagonist. Furthermore, dopamine (100 μM) promoted process formation, which was inhibited by a β-antagonist and enhanced by both an α-antagonist and a D2-like receptor antagonist. In acute hippocampal slices, both a D1-like receptor agonist and β-agonist changed astrocytic morphology. Together, these results indicate that dopamine promotes IL-6 expression and process formation via D1-like receptors and β-adrenoceptors. Furthermore, bidirectional regulation exists; namely, the effects of D1-like receptors and β-adrenoceptors were negatively regulated by D2-like receptors and α2-adrenoceptors.

Keywords

Adrenoceptor; Astrocyte; CREB; Dopamine; IL-6; Morphology.

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