Role of NHE isoforms in mediating bicarbonate reabsorption along the nephron

• Published in: American journal of physiology. Renal physiology Vol. 281; no. 6; p. F1117
• Main Authors: Wang, T, Hropot, M, Aronson, P S, Giebisch, G
• Format: Journal Article
• Language: English
• Published: United States 01-12-2001
• Subjects: Absorption; Amiloride - analogs & derivatives; Amiloride - pharmacology; Animals; Bicarbonates - metabolism; Biological Transport; Culture Techniques; Guanidines - pharmacology; Kidney Tubules, Distal - drug effects; Kidney Tubules, Distal - metabolism; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - metabolism; Loop of Henle - drug effects; Loop of Henle - metabolism; Male; Methacrylates - pharmacology; Rats; Rats, Sprague-Dawley; Sodium-Hydrogen Exchanger 3; Sodium-Hydrogen Exchangers - antagonists & inhibitors; Sodium-Hydrogen Exchangers - physiology; Sulfones - pharmacology
• ISSN: 1931-857X
• DOI: 10.1152/ajprenal.2001.281.6.f1117

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 inhibition 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 HCO(3)(-) (J(HCO3)) were studied by in situ microperfusion. In the proximal tubule, addition of ethylisopropylamiloride or S-3226 significantly reduced J(v) and J(HCO3), but addition of Hoe-694 caused no significant 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 required than what was necessary to inhibit transport in the proximal tubule. In contrast, in the distal convoluted tubule, J(HCO3) was inhibited by Hoe-694 but not by S-3226. These results are consistent with the conclusion that NHE2 rather than NHE3 is the predominant isoform responsible for apical membrane 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.