Role of NHE isoforms in mediating bicarbonate reabsorption along the nephron

This study assessed the functional role of Na+ /H+ exchanger (NHE) isoforms NHE3 and NHE2 in the proximal tubule, loop of Henle, and distal convoluted tubule of the rat kidney by comparing sensitivity of transport to inhibiti on by Hoe-694 (an agent known to inhibit NHE2 but not NHE3) and S-3226 (an agent with much higher affinity for NHE3 than NHE2). Rates of transport of fluid (J(v)) and HCO3- (J(HCO3)) were studied by in situ microperfusion. In the proximal tubule, addition of ethylisopropylamiloride or S-3226 signifi cantly reduced J(v) and J(HCO3), but addition of Hoe-694 caused no signific ant inhibition. In the loop of Henle, J(HCO3) was also inhibited by S-3226 and not by Hoe-694, although much higher concentrations of S-3226 were requ ired than what was necessary to inhibit transport in the proximal tubule. I n contrast, in the distal convoluted tubule, J(HCO3) was inhibited by Hoe-6 94 but not by S-3226. These results are consistent with the conclusion that NHE2 rather than NHE3 is the predominant isoform responsible for apical me mbrane Na+/H+ exchange in the distal convoluted tubule, whereas NHE3 is the predominant apical isoform in the proximal tubule and possibly also in the loop of Henle.