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 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.
Wang
T
T
Department of Cellular and Molecular Physiology, Frankfurt am Main 65926, Germany. tong.wang@yale.edu
Hropot
M
M
Aronson
P S
PS
Giebisch
G
G
D000042:Absorption; D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport; D046508:Culture Techniques; D006146:Guanidines / Q000494:pharmacology; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008138:Loop of Henle / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000502:physiology*; D013450:Sulfones / Q000494:pharmacology
C118956:3-(2-(3-guanidino-2-methyl-3-oxo-propenyl)-5-methylphenyl)-N-isopropylidene-2-methyl-acrylamide dihydrochloride; D001639:Bicarbonates; D006146:Guanidines; D008689:Methacrylates; C513110:Slc9a2 protein, rat; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C074107:3-methylsulfonyl-4-piperidinobenzoyl guanidine; D000584:Amiloride; C039614:ethylisopropylamiloride