We demonstrated that the rapid nongenomic dose-dependent biphasic effect of aldosterone on Na+/H+ exchanger in proximal tubule is compatible with stimulation of this exchanger by small increases in intracellular calcium concentration ([Ca2+]i) (at 10-12 M aldosterone) and inhibition due high increases in [Ca2+]i (at 10-6 M aldosterone) (Leite-Dellova et al, 2008); however, the signaling pathways involved in these effects are still unknown.The purpose of this study is researching the involvement of the mineralocorticoid receptor (MR), glucocorticoid receptor (GR), extracellular signal-regulated Kinases 1 and 2 (ERK1/2), adenosine 3`,5`-monophosphate (cAMP) and protein kinase C (PKC) in the aldosterone rapid effects on the Na+/H+ exchanger and [Ca2+]i of proximal tubule. The hormonal effects on intracellular pH (pHi) and [Ca2+]I were investigate in immortalized proximal tubule cells of rats (IRPTC), using fluorescence microscopy and the probes BCECF-AM (3 µM) and FURA 2-AM (5 µM), respectively. The values shown are means ± S.E.M. and the comparisons are made by ANOVA (p < 0.05). The pHi recovery rate (pHirr), after cellular acidification with a NH4Cl pulse, was 0.24 ± 0.011 pH units/min (N=8). EIPA (20 µM; Na+/H+ exchanger inhibitor) and HOE 694 (5 µM; NHE1 specific inhibitor), but not S3226 (1 µM; NHE3 specific inhibitor), cause a decrease in pHirr (63% and 59%, respectively). The mean baseline [Ca2+]i was 100 ± 4 nM (N=10). Aldosterone (10-12 M; 2 min preincubation) increases the pHirr (50%) and the [Ca2+]i (63%), but aldosterone (10-6 M; 2 min preincubation) decreases the pHirr (46%) and increases the [Ca2+]i (132%). RU 486 (1 µM; GR inhibitor), PD 98059 (15 µM) and U0126 (15 µM) (ERK1/2 inhibitors), Cheleritrine (1 µM) and Stausporine (10-5 M) (PKC inhibitors) abolish the effects of aldosterone on pHirr and [Ca2+]i. Eplerenone (10-5 M, MR inhibitor) and 8Br cAMP (10-5 M; cAMP analogue) do not alter these parameters. The present results confirm our previous data indicating that the rapid biphasic (stimulatory/inhibitory) effect of aldosterone on NHE1 is associated with the rapid stimulatory dose-dependente effect of aldosterone on the [Ca2+]i. The observed effects of aldosterone on pHirr and [Ca2+]i occur via GR (data consistent with GR detection in IRPTC cells by RT-PCR and Western blot) and are mediated by ERK1/2 and PKC signaling pathways and seem to be independent of MR and cAMP. Keywords: aldosterone rapid effects, NHE1, pHi, intracellular calcium