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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, Ile8Ang 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, Ile8Ang 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.
Miura et al. (Thu,) studied this question.