Differential Regulation of the Cell Cycle by α1-Adrenergic Receptor Subtypes

α1-Adrenergic receptors have been implicated in growth-promoting pathways. A microarray study of individual α1-adrenergic receptor subtypes (α1A, α1B, and α1D) expressed in Rat-1 fibroblasts revealed that epinephrine altered the transcription of several cell cycle regulatory genes in a direction consistent with the α1A- and α1D-adrenergic receptors mediating G1-S cell cycle arrest and the α1B-mediating cell-cycle progression. A time course indicated that in α1A cells, epinephrine stimulated a G1-S arrest, which began after 8 h of stimulation and maximized at 16 h, at which point was completely blocked with cycloheximide. The α1B-adrenergic receptor profile also showed unchecked cell cycle progression, even under low serum conditions and induced foci formation. The G1-S arrest induced by α1A- and α1D-adrenergic receptors was associated with decreased cyclin-dependent kinase-6 and cyclin E-associated kinase activities and increased expression of the cyclin-dependent kinase inhibitor p27Kip1, all of which we...