Regulation of alpha 2A-adrenergic receptor mRNA in rat astroglial cultures: role of cyclic AMP and protein kinase C

Abstract

In this study we investigated regulation of alpha 2A-adrenergic receptor (alpha 2A-AR) mRNA in rat astroglial cultures by increases in intracellular cyclic AMP levels and by protein kinase C (PKC) activation. Treatment of astroglial cultures with forskolin (FSK), an adenylyl cyclase activator, or with the membrane-permeable cyclic AMP analogues dibutyryl cyclic AMP or Sp-adenosine 3',5'-cyclic monophosphothioate triethylamine caused time- and concentration-dependent decreases in the levels of a approximately 4.0-kb alpha 2A-AR mRNA transcript. Levels of alpha 2A-AR mRNA were reduced to approximately 10% of control levels within 4 h of 1 microM FSK treatment. PKC agonists [phorbol 12-myristate 13-acetate (PMA), phorbol 12,13-dibutyrate, and mezerein] also decreased alpha 2A-AR mRNA levels in a time- and concentration-dependent fashion. A 90% decrease in alpha 2A-AR mRNA levels was observed with 50 nM PMA in 4 h. The decrease in alpha 2A-AR mRNA levels caused by FSK and PMA treatment appears to be the result of decreases in transcription of the alpha 2A-AR gene and is not due to decreases in alpha 2A-AR mRNA degradation rate. These observations suggest that alpha 2A-AR mRNA levels are regulated by cyclic AMP and PKC.