Mechanism of [Ca2+]i rise induced by angiotensin 1–7 in MDCK renal tubular cells

The effect of angiotensin 1–7 (Ang 1–7) on cytosolic Ca2+ concentrations ([Ca2+]i) in MDCK renal tubular cells was explored. The Ca2+-sensitive fluorescent dye fura-2 was applied to measure [Ca2+]i. Ang 1–7 at concentrations of 10–50 µM induced a [Ca2+]i rise in a concentration-dependent manner. The response was reduced partly by removing Ca2+. Ang 1–7 evoked store operated Ca2+ entry that was inhibited by La3+ and aristolochic acid. In the absence of extracellular Ca2+, incubation with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin prevented Ang 1–7 from releasing more Ca2+. Inhibition of phospholipase C with U73122 abolished Ang 1–7-induced [Ca2+]i rise. Ang 1–7-induced [Ca2+]i rise was abolished by the angiotensin type 1 receptor antagonist losartan, but was not affected by the angiotensin type 2 receptor antagonist PD 123,319. In sum, in MDCK cells, Ang 1–7 stimulated angiotensin type 1 receptors leading to a [Ca2+]i rise that was composed of phospholipase C-dependent Ca2+ release from the...