Norepinephrine activates β 1 -adrenergic receptors at the inner nuclear membrane in astrocytes.

Autor: Benton KC; Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin, USA., Wheeler DS; Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin, USA., Kurtoglu B; Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin, USA., Ansari MBZ; Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin, USA., Cibich DP; Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin, USA., Gonzalez DA; Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin, USA., Herbst MR; Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin, USA., Khursheed S; Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin, USA., Knorr RC; Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin, USA., Lobner D; Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin, USA., Maglasang JG; Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin, USA., Rohr KE; Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin, USA., Taylor A; Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin, USA., Twining RC; Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin, USA., Witt PJ; Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin, USA., Gasser PJ; Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin, USA.
Jazyk: angličtina
Zdroj: Glia [Glia] 2022 Sep; Vol. 70 (9), pp. 1777-1794. Date of Electronic Publication: 2022 May 19.
DOI: 10.1002/glia.24219
Abstrakt: Norepinephrine exerts powerful influences on the metabolic, neuroprotective and immunoregulatory functions of astrocytes. Until recently, all effects of norepinephrine were believed to be mediated by receptors localized exclusively to the plasma membrane. However, recent studies in cardiomyocytes have identified adrenergic receptors localized to intracellular membranes, including Golgi and inner nuclear membranes, and have shown that norepinephrine can access these receptors via transporter-mediated uptake. We recently identified a high-capacity norepinephrine transporter, organic cation transporter 3 (OCT3), densely localized to outer nuclear membranes in astrocytes, suggesting that adrenergic signaling may also occur at the inner nuclear membrane in these cells. Here, we used immunofluorescence and western blot to show that β 1 -adrenergic receptors are localized to astrocyte inner nuclear membranes; that key adrenergic signaling partners are present in astrocyte nuclei; and that OCT3 and other catecholamine transporters are localized to astrocyte plasma and nuclear membranes. To test the functionality of nuclear membrane β 1 -adrenergic receptors, we monitored real-time protein kinase A (PKA) activity in astrocyte nuclei using a fluorescent biosensor. Treatment of astrocytes with norepinephrine induced rapid increases in PKA activity in the nuclear compartment. Pretreatment of astrocytes with inhibitors of catecholamine uptake blocked rapid norepinephrine-induced increases in nuclear PKA activity. These studies, the first to document functional adrenergic receptors at the nuclear membrane in any central nervous system cell, reveal a novel mechanism by which norepinephrine may directly influence nuclear processes. This mechanism may contribute to previously described neuroprotective, metabolic and immunoregulatory actions of norepinephrine.
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Databáze: MEDLINE