Fig. 1B indicates

that the addition of ALDO at 10−12 M to the bath increased the pHirr. However, Fig. 1C shows that the addition of ALDO at 10−6 M Navitoclax price decreased the pHirr, and pHi recovery was not complete. Fig. 2A shows a representative experiment to indicate that with ANP (10−6 M) alone, the pHirr and the final pHi were not different from the control value. However, Fig. 2B and C shows that ANP impaired both the stimulatory and inhibitory effects of ALDO on the pHirr (and during both situations, the final pHi was not different from the basal value). Fig. 3 shows that in the control situation (140 mM Na+e) the mean pHirr was 0.195 ± 0.012 pH units/min (16/96), and the superfusion of tubules with HOE 694 alone inhibited the pHirr, indicating that the pHirr

is mostly due to the basolateral NHE1 in S3 segments. In addition, Fig. 3 shows that in the absence of Na+e (a condition that inhibits the activity of Na+/H+ exchanger), there was a significantly lower pHirr, indicating that a Na+-independent H+ extrusion mechanism exists in the S3 segment of normal rats. This small pHirr was abolished by concanamycin, showing that the H+-ATPase is the only mechanism responsible for this Na+-independent click here H+ transport. However, this mechanism of cellular extrusion of H+ initiates about 2.5 min after cellular acidification with the NH4Cl pulse. Fig. 4 indicates that 10−12 M ALDO increased the pHirr by approximately 59% of the control value, and 10−6 M ALDO decreased it by approximately 49% heptaminol of the control value. Spironolactone alone

did not alter the pHirr and did not prevent the stimulatory and the inhibitory effects of ALDO on the Na+/H+ exchanger, demonstrating that this rapid biphasic effect of ALDO is independent of binding with the MR receptor. RU 486 alone decreased the pHirr (approximately 39% of control value); in addition, RU 486 abolished the stimulatory effect of ALDO but did not alter its inhibitory effect on the Na+/H+ exchanger. These results suggest that the GR antagonism interferes with the nongenomic stimulatory effect of ALDO on the Na+/H+ exchanger. Fig. 4 also shows that, compared to the control, ANP or BAPTA alone did not significantly alter the pHirr; however, ANP or BAPTA significantly abolished both stimulatory and inhibitory effects of ALDO on the pHirr. Table 2 summarizes the mean values of pHi and pHirr responses found in all experimental groups studied. Fig. 5 gives the cell calcium fluorescent signal tracing during 3 min in one representative experiment from each of 6 experimental groups. The images were continuously acquired (at time intervals of 2 s) before and after the addition of different drug solutions to the bath. The baseline value did not significantly change. However, approximately 0.4 min after the addition of ALDO (10−12 M or 10−6 M), there was a transient (approximately 1.