ANGIOTENSIN-II ELEVATES CYTOSOLIC-FREE CALCIUM IN HUMAN LUNG ADENOCARCINOMA CELLS VIA ACTIVATION OF AT(1) RECEPTORS

Angiotensin II (Ang II), bradykinin (BK), and endothelin-1 (ET-1) evoked alterations in cytosolic free calcium, [Ca2+](i), levels were determined using fura-2 fluorescence methodology in a human lung adenocarcinoma cell line (A549), a non-neoplastic lung cell line and a small cell lung carcinoma cell (SCLC) line. Ang II and BK evoked a rapid, concentration-dependent transient increase in [Ca2+](i) in A549 cells. The peak [Ca2+](i) increases attained with Ang II (1 mu M) and BK (1 mu M) were 3- and 4-fold higher, respectively (P < 0.01) than the basal [Ca2+](i) values. This effect of Ang II was completely abolished by inclusion of losartan (DuP 753), an AT(1) subtype selective antagonist. Removal of extracellular Ca2+ from the incubation medium led to significant diminution of the peak [Ca2+](i) response to Ang II but not to BK. In contrast to Ang II and BK, ET-1 failed to evoke an increase in [Ca2+](i) levels in A549 cells. Neither Ang II nor ET-1 evoked any appreciable increase in [Ca2+](i) levels of non-neoplastic lung cell and SCLC cell lines. These data confirm that the human non-small cell lung cancer cells (A549) selectively express AT(1) subtype receptors for Ang II that are functionally coupled to Ca2+ mobilization from both extra and intracellular sources.