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Signaling Pathways in the Biphasic Effect of ANG II on Na+/H+ Exchanger in T84 Cells
Authors:R.?Musa-Aziz,M.?Oliveira-Souza,M.?Mello-Aires  author-information"  >  author-information__contact u-icon-before"  >  mailto:mmaires@icb.usp.br"   title="  mmaires@icb.usp.br"   itemprop="  email"   data-track="  click"   data-track-action="  Email author"   data-track-label="  "  >Email author
Affiliation:1.Department of Physiology and Biophysics, Instituto de Ciências Biomédicas,University of S?o Paulo,S?o Paulo,Brazil
Abstract:The effect of ANG II on pHi, [Ca2+]i and cell volume was investigated in T84 cells, a cell line originated from colon epithelium, using the probes BCECF-AM, Fluo 4-AM and acridine orange, respectively. The recovery rate of pHi via the Na+/H+ exchanger was examined in the first 2 min following the acidification of pHi with a NH4Cl pulse. In the control situation, the pHi recovery rate was 0.118 ± 0.001 (n = 52) pH units/min and ANG II (10−12 M or 10−9 M) increased this value (by 106% or 32%, respectively) but ANG II (10−7 M) decreased it to 47%. The control [Ca2+]i was 99 ± 4 (n = 45) nM and ANG II increased this value in a dose-dependent manner. The ANG II effects on cell volume were minor and late and should not interfere in the measurements of pHi recovery and [Ca2+]i. To document the signaling pathways in the hormonal effects we used: Staurosporine (a PKC inhibitor), W13 (a calcium-dependent calmodulin antagonist), H89 (a PKA inhibitor) or Econazole (an inhibitor of cytochrome P450 epoxygenase). Our results indicate that the biphasic effect of ANG II on Na+/H+ exchanger is a cAMP-independent mechanism and is the result of: 1) stimulation of the exchanger by PKC signaling pathway activation (at 10−12 – 10−7 M ANG II) and by increases of [Ca2+]i in the lower range (at 10−12 M ANG II) and 2) inhibition of the exchanger at high [Ca2+]i levels (at 10−9 – 10−7 M ANG II) through cytochrome P450 epoxygenase-dependent metabolites of the arachidonic acid signaling pathway.
Keywords:Angiotensin II  Colon cells  T84 cells  Na+/H+ exchanger  Intracellular pH
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