Inhibition of rabbit aortic smooth muscle cell proliferation by selective inhibitors of protein kinase C

Br J Pharmacol. 1995 Apr;114(8):1652-6. doi: 10.1111/j.1476-5381.1995.tb14953.x.


1. We studied the effect of two structurally-related, selective inhibitors of protein kinase C, Ro 31-8220 and Ro 31-7549, on the reinitiation of proliferation in quiescent first passage rabbit aortic smooth muscle cells in response to (a) the direct activator of protein kinase C, phorbol dibutyrate (PDBu), (b) platelet-derived growth factor (PDGF), (c) a combination of PDGF and 5-hydroxytryptamine (5-HT) or (d) serum. 2. Ro 31-8220 and Ro 31-7549 concentration-dependently inhibited proliferation in response to each mitogen. The inhibitory potency (IC50) of Ro 31-8220 and Ro 31-7549, respectively, was similar against proliferation induced by PDBu (0.55 and 1.1 microM), PDGF (0.6 and 0.9 microM), PDGF and 5-HT (0.68 and 1.1 microM), although slightly less against serum (1.7 and 5 microM). The effects of the protein kinase C inhibitors on proliferation could not be ascribed to cytotoxicity. Neither Ro 31-8220 nor Ro 31-7549 (0.3-3 microM) inhibited PDGF receptor tyrosine phosphorylation. 3. The results show that Ro 31-8220 and Ro 31-7549 are potent inhibitors of smooth muscle cell proliferation in response to a direct activator of protein kinase C, the defined growth factors, PDGF and 5-HT, and the complex mixture of mitogens in serum. Protein kinase C activation thus appears to be an important growth transducing mechanism for each of these agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects*
  • Cell Division / drug effects
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology
  • Indoles / pharmacology*
  • Maleimides / pharmacology*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Platelet-Derived Growth Factor / pharmacology
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase C / drug effects
  • Rabbits
  • Serotonin / pharmacology
  • Thymidine / metabolism


  • Enzyme Inhibitors
  • Indoles
  • Maleimides
  • Platelet-Derived Growth Factor
  • Serotonin
  • Protein Kinase C
  • Thymidine
  • Ro 31-8220
  • Ro 31-7549