Mechanism of [Ca~(2+)]_i rise induced by angiotensin 1-7 in MDCK renal tubular cells

摘要

The effect of angiotensin 1-7 (Ang 1-7) on cytosolic Ca~(2+) concentrations ([Ca~(2+)]_i) in MDCK renal tubular cells was explored. The Ca~(2+)-sensitive fluorescent dye fura-2 was applied to measure [Ca2+]i. Ang 1-7 at concentrations of 10-50 M induced a [Ca~(2+)]_i rise in a concentration-dependent manner. The response was reduced partly by removing Ca~(2+). Ang 1-7 evoked store operated Ca~(2+) entry that was inhibited by La ~(3+) and aristolochic acid. In the absence of extracellular Ca ~(2+), incubation with the endoplasmic reticulum Ca~(2+) pump inhibitor thapsigargin prevented Ang 1-7 from releasing more Ca~(2+). Inhibition of phospholipase C with U73122 abolished Ang 1-7-induced [Ca ~(2+)]_i rise. Ang 1-7-induced [Ca~(2+)]_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 [Ca~(2+)]_i rise that was composed of phospholipase C-dependent Ca~(2+) release from the endoplasmic reticulum and Ca ~(2+) entry via phospholipase A2-sensitive store-operated Ca ~(2+) channels.