Angiotensin II-induced MAPK phosphorylation mediated by Ras and/or phospholipase C-dependent phosphorylations but not by protein kinase C phosphorylation in cultured rat vascular smooth muscle cells

Pharmacology. 2007;79(1):27-33. doi: 10.1159/000097539. Epub 2006 Nov 28.

Abstract

Angiotensin II (Ang II) induces a rapid increase in mitogen-activated protein kinase (MAPK) activity through the Ang II type 1 receptor in cultured rat vascular smooth muscle cells (VSMCs). In the present study, we examined the effects of the phospholipase C (PLC) inhibitor U73122, the protein kinase C (PKC) inhibitor GF109203X, and the Ras inhibitor farnesylthiosalicylic acid (FTS) on Ang II-induced activation of p42/p44 MAPKs in cultured VSMCs. Phosphorylation was shown using the Western blot technique with specific phospho-antibodies against MAPK proteins. The PLC inhibitor U73122 abolished the Ang II-induced MAPK activity, while the PKC inhibitor GF109203X only decreased it. There was also an inhibition observed with the Ras inhibitor, FTS on Ang II-induced MAPK activity. These data suggest that Ang II-induced MAPK phosphorylation through the Ang II type 1 receptor could be mediated by Ras and/or PLC-dependent phosphorylations but not by PKC phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Estrenes / pharmacology
  • Farnesol / analogs & derivatives
  • Farnesol / pharmacology
  • Indoles / pharmacology
  • Losartan / pharmacology
  • Male
  • Maleimides / pharmacology
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Phosphorylation / drug effects
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Pyrrolidinones / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Angiotensin, Type 1 / physiology
  • Salicylates / pharmacology
  • Time Factors
  • Type C Phospholipases / antagonists & inhibitors
  • Type C Phospholipases / metabolism*
  • ras Proteins / antagonists & inhibitors
  • ras Proteins / metabolism*

Substances

  • Enzyme Inhibitors
  • Estrenes
  • Indoles
  • Maleimides
  • Pyrrolidinones
  • Receptor, Angiotensin, Type 1
  • Salicylates
  • farnesylthiosalicylic acid
  • Angiotensin II
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Farnesol
  • Protein Kinase C
  • Mitogen-Activated Protein Kinases
  • Type C Phospholipases
  • ras Proteins
  • Losartan
  • bisindolylmaleimide I