Regulation of alpha2A-adrenergic receptor expression by epinephrine in cultured astroglia from rat brain.
Epinephrine (Epi) mediates various physiological effects via alpha2A-adrenergic receptors (alpha2A-ARs). Studies in mice with a point mutation in the gene for alpha2A-AR have shown that these receptors are responsible for the centrally mediated depressor effects of alpha2-AR agonists. These studies underscore the importance of understanding the basic cellular mechanisms involved in the expression of alpha2A-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 alpha2A-AR expression. These cells contain alpha2-ARs, which are predominately of the alpha2A-AR subtype. Our studies have shown that Epi causes a dose- and time-dependent decrease in steady-state levels of alpha2A-AR mRNA and number of alpha2A-ARs, effects that are mediated via alpha1- and beta-adrenergic receptors (alpha1-ARs and beta-ARs). These effects of Epi on alpha2A-AR mRNA and alpha2A-AR number are mimicked by activation of protein kinase C or increases in cellular cyclic AMP, which are intracellular messengers activated by alpha1-ARs and beta-ARs, respectively. Taken together, these results indicate that expression of alpha2A-ARs is regulated in a heterologous manner by Epi, via alpha1-AR- and beta-AR-mediated intracellular pathways.
Reutter
M A
MA
Department of Physiology, College of Medicine, University of Florida, Gainesville 32610, USA.
Richards
E M
EM
Sumners
C
C
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D001921:Brain / Q000166:cytology* / Q000378:metabolism*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D005576:Colforsin; D013755:Tetradecanoylphorbol Acetate; D004837:Epinephrine