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P2Y(2) receptor knock-out mice display normal NaCl absorption in medullary thick ascending limb

Local purinergic signals modulate renal tubular transport. Acute activation of renal epithelial P2 receptors causes inhibition of epithelial transport and thus, should favor increased water and salt excretion by the kidney. So far only a few studies have addressed the effects of extracellular nucleo...

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Autores principales: Marques, Rita D., Praetorius, Helle A., Leipziger, Jens
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3793173/
https://www.ncbi.nlm.nih.gov/pubmed/24130530
http://dx.doi.org/10.3389/fphys.2013.00280
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author Marques, Rita D.
Praetorius, Helle A.
Leipziger, Jens
author_facet Marques, Rita D.
Praetorius, Helle A.
Leipziger, Jens
author_sort Marques, Rita D.
collection PubMed
description Local purinergic signals modulate renal tubular transport. Acute activation of renal epithelial P2 receptors causes inhibition of epithelial transport and thus, should favor increased water and salt excretion by the kidney. So far only a few studies have addressed the effects of extracellular nucleotides on ion transport in the thick ascending limb (TAL). In the medullary thick ascending limb (mTAL), basolateral P2X receptors markedly (~25%) inhibit NaCl absorption. Although this segment does express both apical and basolateral P2Y(2) receptors, acute activation of the basolateral P2Y(2) receptors had no apparent effect on transepithelial ion transport. Here we studied, if the absence of the P2Y(2) receptor causes chronic alterations in mTAL NaCl absorption by comparing basal and AVP-stimulated transepithelial transport rates. We used perfused mouse mTALs to electrically measure NaCl absorption in juvenile (<35 days) and adult (>35 days) male mice. Using microelectrodes, we determined the transepithelial voltage (V(te)) and the transepithelial resistance (R(te)) and thus, transepithelial NaCl absorption (equivalent short circuit current, I'(sc)). We find that mTALs from adult wild type (WT) mice have significantly lower NaCl absorption rates when compared to mTALs from juvenile WT mice. This could be attributed to significantly higher R(te)values in mTALs from adult WT mice. This pattern was not observed in mTALs from P2Y(2) receptor knockout (KO) mice. In addition, adult P2Y(2) receptor KO mTALs have significantly lower V(te)values compared to the juvenile. No difference in absolute I'(sc) was observed when comparing mTALs from WT and KO mice. AVP stimulated the mTALs to similar increases of NaCl absorption irrespective of the absence of the P2Y(2) receptor. No difference was observed in the medullary expression level of NKCC2 in between the genotypes. These data indicate that the lack of P2Y(2) receptors does not cause substantial differences in resting and AVP-stimulated NaCl absorption in mouse mTAL.
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spelling pubmed-37931732013-10-15 P2Y(2) receptor knock-out mice display normal NaCl absorption in medullary thick ascending limb Marques, Rita D. Praetorius, Helle A. Leipziger, Jens Front Physiol Physiology Local purinergic signals modulate renal tubular transport. Acute activation of renal epithelial P2 receptors causes inhibition of epithelial transport and thus, should favor increased water and salt excretion by the kidney. So far only a few studies have addressed the effects of extracellular nucleotides on ion transport in the thick ascending limb (TAL). In the medullary thick ascending limb (mTAL), basolateral P2X receptors markedly (~25%) inhibit NaCl absorption. Although this segment does express both apical and basolateral P2Y(2) receptors, acute activation of the basolateral P2Y(2) receptors had no apparent effect on transepithelial ion transport. Here we studied, if the absence of the P2Y(2) receptor causes chronic alterations in mTAL NaCl absorption by comparing basal and AVP-stimulated transepithelial transport rates. We used perfused mouse mTALs to electrically measure NaCl absorption in juvenile (<35 days) and adult (>35 days) male mice. Using microelectrodes, we determined the transepithelial voltage (V(te)) and the transepithelial resistance (R(te)) and thus, transepithelial NaCl absorption (equivalent short circuit current, I'(sc)). We find that mTALs from adult wild type (WT) mice have significantly lower NaCl absorption rates when compared to mTALs from juvenile WT mice. This could be attributed to significantly higher R(te)values in mTALs from adult WT mice. This pattern was not observed in mTALs from P2Y(2) receptor knockout (KO) mice. In addition, adult P2Y(2) receptor KO mTALs have significantly lower V(te)values compared to the juvenile. No difference in absolute I'(sc) was observed when comparing mTALs from WT and KO mice. AVP stimulated the mTALs to similar increases of NaCl absorption irrespective of the absence of the P2Y(2) receptor. No difference was observed in the medullary expression level of NKCC2 in between the genotypes. These data indicate that the lack of P2Y(2) receptors does not cause substantial differences in resting and AVP-stimulated NaCl absorption in mouse mTAL. Frontiers Media S.A. 2013-10-09 /pmc/articles/PMC3793173/ /pubmed/24130530 http://dx.doi.org/10.3389/fphys.2013.00280 Text en Copyright © 2013 Marques, Praetorius and Leipziger. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Marques, Rita D.
Praetorius, Helle A.
Leipziger, Jens
P2Y(2) receptor knock-out mice display normal NaCl absorption in medullary thick ascending limb
title P2Y(2) receptor knock-out mice display normal NaCl absorption in medullary thick ascending limb
title_full P2Y(2) receptor knock-out mice display normal NaCl absorption in medullary thick ascending limb
title_fullStr P2Y(2) receptor knock-out mice display normal NaCl absorption in medullary thick ascending limb
title_full_unstemmed P2Y(2) receptor knock-out mice display normal NaCl absorption in medullary thick ascending limb
title_short P2Y(2) receptor knock-out mice display normal NaCl absorption in medullary thick ascending limb
title_sort p2y(2) receptor knock-out mice display normal nacl absorption in medullary thick ascending limb
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3793173/
https://www.ncbi.nlm.nih.gov/pubmed/24130530
http://dx.doi.org/10.3389/fphys.2013.00280
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