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• W2020673207 abstract "Intracellular ANG II induces biological effects in nonrenal cells, but it is not known whether it plays a physiological role in renal proximal tubule cells (PTCs). PTCs express angiotensinogen, renin, and angiotensin-converting enzyme mRNAs, suggesting the presence of high levels of intracellular ANG II. We determined if microinjection of ANG II directly in single PTCs increases intracellular calcium concentration ([Ca 2+ ] i ) and, if so, elucidated the cellular mechanisms involved. Changes in [Ca 2+ ] i responses were studied by fluorescence imaging using the Ca 2+ indicator fluo 3. ANG II (1 nM) was microinjected directly in the cells, whereas cell-surface angiotensin type 1 (AT 1 ) receptors were blocked by losartan (10 μM). When ANG II (1 nM) was added to the perfusate, there was a marked increase in [Ca 2+ ] i that was blocked by extracellular losartan. With losartan in the perfusate, intracellular microinjection of ANG II elicited a robust increase in cytoplasmic [Ca 2+ ] i that peaked at 30 s (basal: 2.2 ± 0.3 vs. ANG II: 14.9 ± 0.4 relative fluorescence units; P < 0.01). Chelation of extracellular Ca 2+ with EGTA (2 mM) did not alter microinjected ANG II-induced [Ca 2+ ] i responses (Ca 2+ free + ANG II: 12.3 ± 2.6 relative fluorescence units, not significant vs. ANG II); however, pretreatment with thapsigargin to deplete intracellular Ca 2+ stores or with U-73122 to inhibit phospholipase C (1 μM each) markedly attenuated microinjected ANG II-induced [Ca 2+ ] i responses. Combined microinjection of ANG II and losartan abolished [Ca 2+ ] i responses, whereas a combination of ANG II and PD-123319 had no effect. These data demonstrate for the first time that direct microinjection of ANG II in single PTCs increases [Ca 2+ ] i by stimulating intracellular AT 1 receptors and releases Ca 2+ from intracellular stores, suggesting that intracellular ANG II may play a physiological role in PTC function." @default.
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• W2020673207 date "2006-06-01" @default.
• W2020673207 modified "2023-09-23" @default.
• W2020673207 title "Intracellular ANG II induces cytosolic Ca²⁺mobilization by stimulating intracellular AT₁receptors in proximal tubule cells" @default.
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• W2020673207 doi "https://doi.org/10.1152/ajprenal.00269.2005" @default.
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