TY - JOUR T1 - α<sub>1B</sub>- and α<sub>1D</sub>-Adrenergic Receptors Exhibit Different Requirements for Agonist and Mitogen-Activated Protein Kinase Activation to Regulate Growth Responses in Rat 1 Fibroblasts JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 83 LP - 90 DO - 10.1124/jpet.300.1.83 VL - 300 IS - 1 AU - Bruce A. Waldrop AU - Diana Mastalerz AU - Michael T. Piascik AU - Ginell R. Post Y1 - 2002/01/01 UR - http://jpet.aspetjournals.org/content/300/1/83.abstract N2 - We compared DNA replication, protein biosynthesis, and mitogen-activated protein kinase (MAPK) activity in Rat 1 fibroblasts stably expressing either the α1B-adrenergic receptor (AR) or α1D-AR subtypes. Activation of both the α1B-AR and α1D-AR inhibited DNA synthesis (as assessed by [3H]thymidine incorporation). In contrast, both receptors stimulated protein biosynthesis (as measured by [35S]methionine incorporation) and activated extracellular signal-regulated kinase (ERK)1/2. Importantly, these responses were agonist-dependent for the α1B-AR, but were agonist-independent for the α1D-AR. Agonist activation of the α1B-AR resulted in increased p38 kinase activity, but not c-Jun NH2-terminal kinase (JNK) activity, whereas the α1D-AR activated JNK but not p38 kinase. Unlike ERK1/2, JNK activity was increased by agonist treatment in the α1D-AR cells. An ERK1/2-pathway inhibitor PD98059 had no effect on phenylephrine-mediated inhibition of DNA synthesis in either cell line but blocked protein biosynthesis mediated by both receptors. The p38 kinase inhibitor SB203580 blocked α1B-AR effects on [3H]thymidine and [35S]methionine incorporation in α1B-AR-expressing cells, but had no effect on α1D-AR-mediated growth responses, consistent with the inability of the α1D-AR to activate p38 kinase. Therefore, α1B- and α1D-ARs mediated similar growth responses but differ with respect to the MAPK family member involved and the requirement for agonist. ARadrenergic receptorMAPKmitogen-activated protein kinaseERKextracellular signal-regulated kinaseJNKc-Jun NH2-terminal kinaseDMEMDulbecco's modified Eagle's mediumFBSfetal bovine serumPEphenylephrinePBSphosphate-buffered salineGSTglutathioneS-transferaseMBPmyelin basic proteinIODintegrated optical densityDMSOdimethyl sulfoxidePAGEpolyacrylamide gel electrophoresisCHOChinese hamster ovarySBSB203580 ER -