Increasing cAMP antagonizes hypertrophic response to angiotensin II without affecting Ras and MAP kinase activation in vascular smooth muscle cells.
Angiotensin II (Ang II), a potent hypertrophic factor for vascular smooth muscle cells (VSMC), induces activation of the ras proto-oncogene product (Ras) and mitogen-activated protein (MAP) kinases, and tyrosine phosphorylation of a focal adhesion-associated protein, paxillin. Forskolin, a direct activator of adenylate cyclase, and dibutyryl cAMP (Bt2 cAMP), a membrane permeable cAMP analogue, potently inhibited Ang II-stimulated protein synthesis. However, they did not inhibit Ang II-induced activation of Ras and MAP kinases. Although both forskolin and Bt2 cAMP potently reduced background tyrosine phosphorylation of paxillin, they allowed Ang II to induce the same reaction. These results indicate that increasing cAMP antagonizes the hypertrophic response to Ang II without affecting Ras and MAP kinase activation in VSMC and suggest that it does not interrupt signaling from the Ang II receptor to focal adhesions.
Takahashi
T
T
Department of Internal Medicine (1st Division), Kobe University School of Medicine, Japan.
Kawahara
Y
Y
Okuda
M
M
Yokoyama
M
M
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D051381:Rats; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D051419:Paxillin; D010750:Phosphoproteins; C496063:Pxn protein, rat; D000804:Angiotensin II; D005576:Colforsin; D003994:Bucladesine; D004247:DNA; D000242:Cyclic AMP; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018631:ras Proteins