Alpha1-adrenoceptor subtype activation increases proto-oncogene mRNA levels. Role of protein kinase C

Eur J Pharmacol. 1998 Jan 26;342(2-3):311-7. doi: 10.1016/s0014-2999(97)01465-9.

Abstract

Noradrenaline increased the mRNA levels of c-fos and c-jun in rat-1 fibroblast lines stably expressing the cloned alpha1-adrenoceptor subtypes. The efficacy to induce the expression of c-fos mRNA was similar for the three cell lines (alpha1d = alpha1b = alpha1a) but different for c-jun (alpha1a > or = alpha1b > alpha1d). The EC50 values were also different: approximately 5 nM (c-fos) and approximately 300 nM (c-jun) for cells transfected with the alpha1a subtype, approximately 30 nM (c-fos) and approximately 300 nM (c-jun) for cells transfected with the alpha1b subtype and approximately 300 nM (c-fos and c-jun) for those transfected with the alpha1d subtype. Staurosporine and protein kinase C down-regulation blocked such effects, indicating a role of this protein kinase. Endothelin-1 (10 nM) also increased the levels of c-fos and c-jun mRNAs. These actions of endothelin-1 were unaffected by staurosporine and protein kinase C down-regulation. It is concluded that activation of any of the three cloned subtypes can increase the levels of c-fos and c-jun mRNAs and that protein kinase C plays a major role in mediating such effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Animals
  • Autoradiography
  • Blotting, Western
  • Cells, Cultured
  • Down-Regulation / drug effects
  • Endothelin-1 / biosynthesis
  • Enzyme Induction / drug effects
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Norepinephrine / pharmacology
  • Protein Kinase C / biosynthesis*
  • Proto-Oncogene Proteins c-fos / biosynthesis*
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-jun / biosynthesis*
  • Proto-Oncogene Proteins c-jun / genetics
  • RNA, Messenger / biosynthesis*
  • Rats
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Staurosporine / pharmacology

Substances

  • Adrenergic alpha-Agonists
  • Endothelin-1
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • Receptors, Adrenergic, alpha-1
  • Protein Kinase C
  • Staurosporine
  • Norepinephrine