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

Abstract

Angiotensin II (Ang II) increases intracellular calcium concentration ([Ca 2+] i) in both normal and cancerous human breast cells in primary culture. Maximal [Ca 2+] i increase is obtained using 100 nM Ang II in both cell types; in cancerous breast cells, [Ca 2+] i increase (Δ[Ca 2+] 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 Ca 2+ transient peak mediated by thapsigargin (TG) sensitive stores; neither Ca 2+ entry through L-type membrane channels or capacitative Ca 2+ entry are involved. Type I Ang II receptor subtype (AT1) mediates Ang II-dependent [Ca 2+] i increase, since losartan, an AT1 inhibitor, blunted [Ca 2+] 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 [Ca 2+] i transient peak in a dose-dependent mode. Thus, the present study provides new information about Ca 2+ signaling pathways mediated through AT1 in breast cells in which no data were yet available.