Back to Search
Start Over
Genetic knockout and pharmacologic inhibition of NCX2 cause natriuresis and hypercalciuria.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2015 Jan 09; Vol. 456 (2), pp. 670-5. Date of Electronic Publication: 2014 Dec 11. - Publication Year :
- 2015
-
Abstract
- The Na(+)/Ca(2+) exchanger (NCX) is a bidirectional transporter that is controlled by membrane potential and transmembrane gradients of Na(+) and Ca(2+). Although two isoforms of NCX1 and NCX2 are coexpressed on the basolateral membrane of the distal nephron, the functional significance of these isoforms is not entirely clear. Therefore, we used NCX1- and NCX2-heterozygote knockout mice (KO) and their double KO, as well as isoform-selective NCX inhibitors, to determine the roles of NCX isoforms in urine formation and electrolyte excretion in mice. NCX inhibitors, particularly NCX2-sensitive inhibitors, caused a dose-dependent natriuresis and in a higher dose, moreover, hypercalciuria. Consistently, NCX1-KO possessed normal renal function similar to wild-type mice (WT), whereas NCX2-KO and double KO exhibited moderate natriuresis and hypercalciuria. Notably, renal responses to YM-244769 were equivalently observed in NCX1-KO and WT, but disappeared in NCX2-KO and double KO. Thus, functional inhibition of NCX2 initially causes natriuresis, and further inhibition of NCX2 produces hypercalciuria, suggesting that the functional significance of NCX2 lies in Na(+) and Ca(2+) reabsorption of the kidney.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Aniline Compounds pharmacology
Animals
Gene Knockout Techniques
Hypercalciuria genetics
Kidney metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Natriuresis drug effects
Natriuresis genetics
Niacinamide analogs & derivatives
Niacinamide pharmacology
Phenyl Ethers pharmacology
Protein Isoforms antagonists & inhibitors
Protein Isoforms genetics
Protein Isoforms metabolism
Sodium-Calcium Exchanger antagonists & inhibitors
Sodium-Calcium Exchanger genetics
Thiourea analogs & derivatives
Thiourea pharmacology
Hypercalciuria physiopathology
Natriuresis physiology
Sodium-Calcium Exchanger metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 456
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 25498502
- Full Text :
- https://doi.org/10.1016/j.bbrc.2014.12.016