Hyposmolality stimulates apical membrane Na+/H+ exchange and HCO3 - absorption in renal thick ascending limb

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The regulation of epithelial Na+/H+ exchangers (NHEs) by hyposmolality is poorly understood. In the renal medullary thick ascending limb (MTAL), transepithelial bicarbonate (HCO3 -) absorption is mediated by apical membrane Na+/H+ exchange, attributable to NHE3. In the present study we examined the effects of hyposmolality on apical Na+/H+ exchange activity and HCO3 - absorption in the MTAL of the rat. In MTAL perfused in vitro with 25 mM HCO3 - solutions, decreasing osmolality in the lumen and bath by removal of either mannitol or sodium chloride significantly increased HCO3 - absorption. The responses to lumen addition of the inhibitors ethylisopropyl amiloride, amiloride, or HOE 694 are consistent with hyposmotic stimulation of apical NHE3 activity and provide no evidence for a role for apical NHE2 in HCO3 - absorption. Hyposmolality increased apical Na+/H+ exchange activity over the phi range 6.5-7.5 due to an increase in V(max). Pretreatment with either tyrosine kinase inhibitors or with the tyrosine phosphatase inhibitor molybdate completely blocked stimulation of HCO3 - absorption by hyposmolality. These results demonstrate that hyposmolality increases HCO3 - absorption in the MTAL through a novel stimulation of apical membrane Na+/H+ exchange and provide the first evidence that NHE3 is regulated by hyposmotic stress. Stimulation of apical Na+/H+ exchange activity in renal cells by a decrease in osmolality may contribute to such pathophysiological processes as urine acidification by diuretics, diuretic resistance, and renal sodium retention in edematous states.

Original languageEnglish
Pages (from-to)1593-1602
Number of pages10
JournalJournal of Clinical Investigation
Volume104
Issue number11
StatePublished - Dec 1999

Fingerprint

Extremities
Membranes
Amiloride
Kidney
Diuretics
Osmolar Concentration
Sodium-Hydrogen Antiporter
Mannitol
Bicarbonates
Baths
Phosphoric Monoester Hydrolases
Sodium Chloride
Protein-Tyrosine Kinases
Tyrosine
Renal Reabsorption
Sodium
Urine

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{0cd6dd74585f4cfaa7f366059edece29,
title = "Hyposmolality stimulates apical membrane Na+/H+ exchange and HCO3 - absorption in renal thick ascending limb",
abstract = "The regulation of epithelial Na+/H+ exchangers (NHEs) by hyposmolality is poorly understood. In the renal medullary thick ascending limb (MTAL), transepithelial bicarbonate (HCO3 -) absorption is mediated by apical membrane Na+/H+ exchange, attributable to NHE3. In the present study we examined the effects of hyposmolality on apical Na+/H+ exchange activity and HCO3 - absorption in the MTAL of the rat. In MTAL perfused in vitro with 25 mM HCO3 - solutions, decreasing osmolality in the lumen and bath by removal of either mannitol or sodium chloride significantly increased HCO3 - absorption. The responses to lumen addition of the inhibitors ethylisopropyl amiloride, amiloride, or HOE 694 are consistent with hyposmotic stimulation of apical NHE3 activity and provide no evidence for a role for apical NHE2 in HCO3 - absorption. Hyposmolality increased apical Na+/H+ exchange activity over the phi range 6.5-7.5 due to an increase in V(max). Pretreatment with either tyrosine kinase inhibitors or with the tyrosine phosphatase inhibitor molybdate completely blocked stimulation of HCO3 - absorption by hyposmolality. These results demonstrate that hyposmolality increases HCO3 - absorption in the MTAL through a novel stimulation of apical membrane Na+/H+ exchange and provide the first evidence that NHE3 is regulated by hyposmotic stress. Stimulation of apical Na+/H+ exchange activity in renal cells by a decrease in osmolality may contribute to such pathophysiological processes as urine acidification by diuretics, diuretic resistance, and renal sodium retention in edematous states.",
author = "Watts, {Bruns A.} and Good, {David W.}",
year = "1999",
month = "12",
language = "English",
volume = "104",
pages = "1593--1602",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "11",

}

TY - JOUR

T1 - Hyposmolality stimulates apical membrane Na+/H+ exchange and HCO3 - absorption in renal thick ascending limb

AU - Watts, Bruns A.

AU - Good, David W.

PY - 1999/12

Y1 - 1999/12

N2 - The regulation of epithelial Na+/H+ exchangers (NHEs) by hyposmolality is poorly understood. In the renal medullary thick ascending limb (MTAL), transepithelial bicarbonate (HCO3 -) absorption is mediated by apical membrane Na+/H+ exchange, attributable to NHE3. In the present study we examined the effects of hyposmolality on apical Na+/H+ exchange activity and HCO3 - absorption in the MTAL of the rat. In MTAL perfused in vitro with 25 mM HCO3 - solutions, decreasing osmolality in the lumen and bath by removal of either mannitol or sodium chloride significantly increased HCO3 - absorption. The responses to lumen addition of the inhibitors ethylisopropyl amiloride, amiloride, or HOE 694 are consistent with hyposmotic stimulation of apical NHE3 activity and provide no evidence for a role for apical NHE2 in HCO3 - absorption. Hyposmolality increased apical Na+/H+ exchange activity over the phi range 6.5-7.5 due to an increase in V(max). Pretreatment with either tyrosine kinase inhibitors or with the tyrosine phosphatase inhibitor molybdate completely blocked stimulation of HCO3 - absorption by hyposmolality. These results demonstrate that hyposmolality increases HCO3 - absorption in the MTAL through a novel stimulation of apical membrane Na+/H+ exchange and provide the first evidence that NHE3 is regulated by hyposmotic stress. Stimulation of apical Na+/H+ exchange activity in renal cells by a decrease in osmolality may contribute to such pathophysiological processes as urine acidification by diuretics, diuretic resistance, and renal sodium retention in edematous states.

AB - The regulation of epithelial Na+/H+ exchangers (NHEs) by hyposmolality is poorly understood. In the renal medullary thick ascending limb (MTAL), transepithelial bicarbonate (HCO3 -) absorption is mediated by apical membrane Na+/H+ exchange, attributable to NHE3. In the present study we examined the effects of hyposmolality on apical Na+/H+ exchange activity and HCO3 - absorption in the MTAL of the rat. In MTAL perfused in vitro with 25 mM HCO3 - solutions, decreasing osmolality in the lumen and bath by removal of either mannitol or sodium chloride significantly increased HCO3 - absorption. The responses to lumen addition of the inhibitors ethylisopropyl amiloride, amiloride, or HOE 694 are consistent with hyposmotic stimulation of apical NHE3 activity and provide no evidence for a role for apical NHE2 in HCO3 - absorption. Hyposmolality increased apical Na+/H+ exchange activity over the phi range 6.5-7.5 due to an increase in V(max). Pretreatment with either tyrosine kinase inhibitors or with the tyrosine phosphatase inhibitor molybdate completely blocked stimulation of HCO3 - absorption by hyposmolality. These results demonstrate that hyposmolality increases HCO3 - absorption in the MTAL through a novel stimulation of apical membrane Na+/H+ exchange and provide the first evidence that NHE3 is regulated by hyposmotic stress. Stimulation of apical Na+/H+ exchange activity in renal cells by a decrease in osmolality may contribute to such pathophysiological processes as urine acidification by diuretics, diuretic resistance, and renal sodium retention in edematous states.

UR - http://www.scopus.com/inward/record.url?scp=0033452789&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033452789&partnerID=8YFLogxK

M3 - Article

C2 - 10587523

AN - SCOPUS:0033452789

VL - 104

SP - 1593

EP - 1602

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 11

ER -