Increasing cAMP antagonizes hypertrophic response to angiotensin II without affecting Ras and MAP kinase activation in vascular smooth muscle cells

FEBS Letters

Okuda, Masanori¹  Kawahara, Yasuhiro¹  Takahashi, Tomosaburo¹  Yokoyama, Mitsuhiro¹ 

[1] Department of Internal Medicine (1st Division), Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650, Japan

关键词: Angiotensin II;    Hypertrophy;    cAMP;    Ras;    MAP kinase;    Vascular smooth muscle cell;   

DOI  :  10.1016/S0014-5793(96)01145-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown