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.
Copyright (c) 2007 S. Karger AG, Basel.
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