AT1 Angiotensin II receptor mediates intracellular calcium mobilization in normal and cancerous breast cells in primary culture

Angiotensin II (Ang II) increases intracellular calcium concentration ([Ca2+](i)) in both normal and cancerous human breast cells in primary culture. Maximal [Ca2+](i) increase is obtained using 100nM Ang II in both cell types; in cancerous breast cells, [Ca2+](i) increase (Delta[Ca2+](i)) is 135 +/- 10 nM, while in normal breast cells it reaches 65 +/- 5 nM (P < 0.0001). In both cell types, Ang II evokes a Ca2+ transient peak mediated by thapsigargin (TG) sensitive stores; neither Ca2+ entry through L-type membrane channels or capacitative Ca2+ entry are involved. Type I Ang II receptor subtype (AT1) mediates Ang II-dependent [Ca2+](i) increase, since losartan, an AT1 inhibitor, blunted [Ca2+](i) increase induced by Ang II in a dose-dependent manner, while CGP 4221A, an AT2 inhibitor, does not. Phospholipase C (PLC) is involved in this signaling mechanism, as U73122, a PLC inhibitor, decreases Ang II-dependent [Ca2+](i) transient peak in a dose-dependent mode. Thus, the present study provides new information about Ca2+ signaling pathways mediated through AT1 in breast cells in which no data were yet available.