α1B- and α1D-adrenergic receptors exhibit different requirements for agonist and mitogen-activated protein kinase activation to regulate growth responses in Rat 1 fibroblasts

Bruce A. Waldrop, Diana Mastalerz, Michael T. Piascik, Ginell R. Post

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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 ceils, 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.

Original languageEnglish
Pages (from-to)83-90
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume300
Issue number1
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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