Regulation of ethanol-sensitive EAAT2 expression through adenosine A1 receptor in astrocytes |
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| Authors: | Wu Jinhua Lee Moonnoh R Kim Taehyun Johng Sandy Rohrback Suzanne Kang Nayoung Choi Doo-Sup |
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| Affiliation: | aDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN, USA;bDepartment of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA;cDepartment of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA |
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| Abstract: | Adenosine-regulated glutamate signaling in astrocytes is implicated in many neurological and neuropsychiatric disorders. In this study, we examined whether adenosine A1 receptor regulates EAAT2 expression in astrocytes using pharmacological agents and siRNAs. We found that adenosine A1 receptor-specific antagonist DPCPX or PSB36 decreased EAAT2 expression in a dose-dependent manner. Consistently, knockdown of A1 receptor in astrocytes decreased EAAT2 mRNA expression while overexpression of A1 receptor upregulated EAAT2 expression and function. Since A1 receptor activation is mainly coupled to inhibitory G-proteins and inhibits the activity of adenylate cyclase, we investigated the effect of forskolin, which activates adenylate cyclase activity, on EAAT2 mRNA levels. Interestingly, we found that forskolin reduced EAAT2 expression in dose- and time-dependent manners. In contrast, adenylate cyclase inhibitor SQ22536 increased EAAT2 expression in dose- and time-dependent manners. In addition, forskolin blocked ethanol-induced EAAT2 upregulation. Taken together, these results suggest that A1 receptor-mediated signaling regulates EAAT2 expression in astrocytes. |
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| Keywords: | EAAT2 Glutamate Adenosine A1 receptor Adenylate cyclase Astrocytes Alcoholism |
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