Angiotensin II type 1 receptor-mediated increase in cytosolic Ca2+ and proliferation in mesothelial cells

We investigated the Ca2+ signaling pathways of the response to angiotensin YI in pleural mesothelial cells and the role of these Ca2+ signaling pathwa ys in mesothelial cell proliferation. Rat pleural mesothelial cells were ma intained in vitro, and the Ca2+ movement to angiotensin II was evaluated us ing the fluorescent Ca2+ indicator fura 2. Furthermore, proliferation of me sothelial cells was assessed using a spectrophotometric 3-(4,5-dimethylthaz ol-2-yl)-2,5-diphenyl-2H-tetrasodium bromide (MMT) assay. Angiotensin II (1 pM-100 mu M) induced in mesothelial cells a biphasic elevation of intracel lular Ca2+ concentration ([Ca2+](i)) that consisted of a transient initial component, followed by a sustained component. Neither removal of extracellu lar Ca2+ nor inhibition of Ca2+ influx by 1 mu M nifedipine affected the an giotensin II-induced initial transient elevation of [Ca2+](i) in mesothelia l cells. Nifedipine did not block angiotensin II-induced sustained elevatio n of [Ca2+](i). Angiotensin II (1 pM-100 mu M) had a proliferative effect o n mesothelial cells in a dose-dependent manner. Angiotensin II type 1 (AT(1 )) receptor antagonist ([Sar(1), Ile(8)]angiotensin II) inhibited both angi otensin II-induced elevation of [Ca2+](i) and proliferation of mesothelial cells. Pertussis toxin did not affect angiotensin II-induced responses. The se results suggest that angiotensin II-induced responses to mesothelial cel ls are extremely dependent on the angiotensin AT(1) receptor coupled with p ertussis toxin-insensitive G protein. (C) 2000 Elsevier Science B.V. All ri ghts reserved.