Hypertension Research
Online ISSN : 1348-4214
Print ISSN : 0916-9636
ISSN-L : 0916-9636
Experimental studies
Activation of Extracellular Signal-Activated Kinase by Angiotensin II-Induced Gq-Independent Epidermal Growth Factor Receptor Transactivation
Shin-ichiro MIURAJingli ZHANGYoshino MATSUOKeijiro SAKUSadashiva S. KARNIK
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2004 Volume 27 Issue 10 Pages 765-770


Multiple signaling pathways link the angiotensin II (Ang II) type 1 (AT1) receptor to Gq-dependent inositol phosphate (IP) production and Gq-independent phospho-extracellular signal-activated kinase (p-ERK) 1/2 activation by Ang II in the regulation of cardiovascular vasoconstriction and cell growth, respectively. An Ang II analogue, [Sar1, Ile4, Ile8]Ang II, did not stimulate Gq-dependent IP production, but still activated Gq-independent p-ERK1/2 in human coronary artery smooth muscle cells as well as in a cell line that stably expressed AT1. This activation was mostly mediated by [Sar1, Ile4, Ile8]Ang II-induced Gq-independent epidermal growth factor receptor transactivation. We found that AT1 receptor signaling shows bifurcation into functionally separate pathways. A clear understanding of this unique signaling may be necessary for the development of therapeutic agents to treat disorders such as hypertension and cardiac hypertrophy. (Hypertens Res 2004; 27: 765-770)

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© 2004 by the Japanese Society of Hypertension
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