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Novel amiloride-sensitive sodium-dependent proton secretion in the mouse proximal convoluted tubule.

Authors
 Joo Young Choi  ;  Mehul Shah  ;  Min Goo Lee  ;  Patrick J. Schultheis  ;  Gary E. Shull  ;  Shmuel Muallem  ;  Michel Baum 
Citation
 Journal of Clinical Investigation, Vol.105(8) : 1141-1146, 2000 
Journal Title
 Journal of Clinical Investigation 
ISSN
 0021-9738 
Issue Date
2000
MeSH
Amiloride/analogs & derivatives ; Amiloride/pharmacology ; Animals ; Guanidines/pharmacology ; Kidney Tubules, Proximal/drug effects ; Kidney Tubules, Proximal/metabolism ; Kidney Tubules, Proximal/secretion* ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Protons* ; Sodium/metabolism ; Sodium-Hydrogen Exchanger 3 ; Sodium-Hydrogen Exchangers/genetics ; Sodium-Hydrogen Exchangers/metabolism* ; Sulfones/pharmacology
Abstract
The proximal convoluted tubule (PCT) reabsorbs most of the filtered bicarbonate. Proton secretion is believed to be mediated predominantly by an apical membrane Na(+)/H(+) exchanger (NHE). Several NHE isoforms have been cloned, but only NHE3 and NHE2 are known to be present on the apical membrane of the PCT. Here we examined apical membrane PCT sodium-dependent proton secretion of wild-type (NHE3(+/+)/NHE2(+/+)), NHE3(-/-), NHE2(-/-), and double-knockout NHE3(-/-)/NHE2(-/-) mice to determine their relative contribution to luminal proton secretion. NHE2(-/-) and wild-type mice had comparable rates of sodium-dependent proton secretion. Sodium-dependent proton secretion in NHE3(-/-) mice was approximately 50% that of wild-type mice. The residual sodium-dependent proton secretion was inhibited by 100 microM 5-(N-ethyl-N-isopropyl) amiloride (EIPA). Luminal sodium-dependent proton secretion was the same in NHE3(-/-)/NHE2(-/-) as in NHE3(-/-) mice. These data point to a previously unrecognized Na(+)-dependent EIPA-sensitive proton secretory mechanism in the proximal tubule that may play an important role in acid-base homeostasis.
Files in This Item:
T200002486.pdf Download
DOI
10.1172/JCI9260
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/171687
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