Regulation of α2A‐Adrenergic Receptor Expression by Epinephrine in Cultured Astroglia from Rat Brain

Abstract: Epinephrine (Epi) mediates various physiological effects via α 2A ‐adrenergic receptors (α 2A ‐ARs). Studies in mice with a point mutation in the gene for α 2A ‐AR have shown that these receptors are responsible for the centrally mediated depressor effects of α 2 ‐AR agonists. These studies underscore the importance of understanding the basic cellular mechanisms involved in the expression of α 2A ‐ARs, of which little is known. We use astroglia cultured from the hypothalamus and brainstem of adult Sprague‐Dawley rats as a model system in which to study factors that regulate α 2A ‐AR expression. These cells contain α 2 ‐ARs, which are predominately of the α 2A ‐AR subtype. Our studies have shown that Epi causes a dose‐ and time‐dependent decrease in steady‐state levels of α 2A ‐AR mRNA and number of α 2A ‐ARs, effects that are mediated via α 1 ‐ and β‐adrenergic receptors (α 1 ‐ARs and β‐ARs). These effects of Epi on α 2A ‐AR mRNA and α 2A ‐AR number are mimicked by activation of protein kinase C or increases in cellular cyclic AMP, which are intracellular messengers activated by α 1 ‐ARs and β‐ARs, respectively. Taken together, these results indicate that expression of α 2A ‐ARs is regulated in a heterologous manner by Epi, via α 1 ‐AR‐ and β‐AR‐mediated intracellular pathways.