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Increasing cAMP antagonizes hypertrophic response to angiotensin II without affecting Ras and MAP kinase activation in vascular smooth muscle cells
Author(s) -
Takahashi Tomosaburo,
Kawahara Yasuhiro,
Okuda Masanori,
Yokoyama Mitsuhiro
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(96)01145-3
Subject(s) - forskolin , angiotensin ii , medicine , endocrinology , paxillin , mitogen activated protein kinase , vascular smooth muscle , activator (genetics) , tyrosine phosphorylation , chemistry , microbiology and biotechnology , protein kinase a , phosphorylation , biology , focal adhesion , receptor , stimulation , smooth muscle , blood pressure
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 (Bt 2 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 Bt 2 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.