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 100 nM Ang II in both cell types; in cancerous breast cells, [Ca2+]i increase (Δ[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 wich no data were yet available.
ASJC Scopus subject areas
- Cell Biology