The effect of angiotensin II (Ang II) on Ca2+ signalling in human primary cultured breast epithelial cells was investigated by using fura-2 as the Ca2+ probe. Ang II (0.1-1000 nM) induced an intracellular free calcium ([Ca2+]i) transient peak which was unchanged by external Ca2+ removal. In Ca2+-free medium pretreatment with thapsigargin abolished Ang II-induced Ca2+ release. Suppression of 1,4,5-inositol trisphosphate formation by U73122, a phospholipase C inhibitor, blocked the Ang II-induced Ca2+ response. Losartan (DuP753), an inhibitor of Ang II type I receptor (AT1), decreased the [Ca2+]i increase evoked by Ang II, while CGP4221A, an inhibitor of Ang II type II receptor (AT2) did not. AT1 desensitisation was demonstrated with respect to the Ca2+ response after subsequent exposure of cells to Ang II and also after pretreatment for 25 min with 1000 nM phorbol 12-myristate 13-acetate. Staurosporine, an inhibitor of protein kinases C (PKC), inhibited the AT1 desensitisation. Epithelial breast cells expressed PKC-α, -β1, -δ and -ζ isozymes, and Ang II provoked translocation from the cytosol to the membranes of PKC-α, -β1, and -δ (but not -ζ). Ang II was also able to stimulate cell proliferation in a dose-dependent manner; this effect was blocked by Gö 6976, a specific inhibitor of PKC-α and -β1, the Ca2+-dependent isozymes. The main conclusion of this study is that the the Ang II signalling mechanism in breast epithelial cells is based on the elevation of [Ca2+]i released from intracellular stores through AT1 activation. In addition, Ang II stimulates cell proliferation by the activation of PKC isozymes.
CITATION STYLE
Greco, S., Muscella, A., Elia, M. G., Salvatore, P., Storelli, C., & Marsigliante, S. (2002). Activation of angiotensin II type I receptor promotes protein kinase C translocation and cell proliferation in human cultured breast epithelial cells. Journal of Endocrinology, 174(2), 205–214. https://doi.org/10.1677/joe.0.1740205
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