Angiotensin II elevates cytosolic free calcium in human lung adenocarcinoma cells via activation of AT1 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 microM) and BK (1 microM) 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 AT1 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 AT1 subtype receptors for Ang II that are functionally coupled to Ca2+ mobilization from both extra and intracellular sources.
Batra
V K
VK
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Gopalakrishnan
V
V
McNeill
J R
JR
Hickie
R A
RA
D000230:Adenocarcinoma / Q000378:metabolism* / Q000648:ultrastructure*; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D002118:Calcium / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000648:ultrastructure; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000648:ultrastructure; D008175:Lung Neoplasms / Q000378:metabolism* / Q000648:ultrastructure*; D011945:Receptors, Angiotensin / Q000378:metabolism / Q000502:physiology*; D018002:Receptors, Bradykinin / Q000378:metabolism / Q000502:physiology; D017466:Receptors, Endothelin / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured
D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin; D018002:Receptors, Bradykinin; D017466:Receptors, Endothelin; D000804:Angiotensin II; D002118:Calcium