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P2X receptors trigger intracellular alkalization in isolated perfused mouse medullary thick ascending limb.

de Bruijn PI, Bleich M, Praetorius HA, Leipziger J - Acta Physiol (Oxf) (2014)

Bottom Line: The renal outer medullary K(+) channel (ROMK) is sensitive to intracellular pH where a reduction leads to closing of ROMK.We speculated that P2X receptor stimulation in the TAL could lead to changes in pHi , leading to a reduction in NaCl transport.Typically, Gq -coupled receptors cause a significant acidification of tubular epithelial cells, which was confirmed in this study, by P2Y2 and Ca(2+) sensing receptor stimulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus C, Denmark.

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Effect of Na+/H+ exchanger (NHE3) inhibition with #4167 on ATP-induced alkalization. (a) Original experiment of perfused medullary thick ascending limb exposed to luminal #4167 (1 μm) and basolateral ATP (100 μm). (b) Summary (ΔpHi) of the series. *Indicates statistical significance P < 0.01, n = 8.
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fig05: Effect of Na+/H+ exchanger (NHE3) inhibition with #4167 on ATP-induced alkalization. (a) Original experiment of perfused medullary thick ascending limb exposed to luminal #4167 (1 μm) and basolateral ATP (100 μm). (b) Summary (ΔpHi) of the series. *Indicates statistical significance P < 0.01, n = 8.

Mentions: A recent study from our group has established that furosemide causes an intracellular alkalization in the mTAL through increased apical NHE3-mediated H+ secretion (de Bruijn et al. 2013). To investigate whether the ATP-induced intracellular alkalization occurs by the same mechanism, basolateral ATP was tested in the presence of the specific NHE3 blocker #4167 (Reuter et al. 2008). Figure5a shows that luminal #4167 (1 μm) caused a significant intracellular acidification (ΔpH −0.35 ± 0.02, n = 8, Fig.5b). During this NHE3 inhibition, the ATP-induced alkalization was completely abolished in five of eight experiments, whereas in three experiments, the alkalization was strongly attenuated. These data indicate that apical NHE3 activity is required for the ATP-induced alkalization.


P2X receptors trigger intracellular alkalization in isolated perfused mouse medullary thick ascending limb.

de Bruijn PI, Bleich M, Praetorius HA, Leipziger J - Acta Physiol (Oxf) (2014)

Effect of Na+/H+ exchanger (NHE3) inhibition with #4167 on ATP-induced alkalization. (a) Original experiment of perfused medullary thick ascending limb exposed to luminal #4167 (1 μm) and basolateral ATP (100 μm). (b) Summary (ΔpHi) of the series. *Indicates statistical significance P < 0.01, n = 8.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4374443&req=5

fig05: Effect of Na+/H+ exchanger (NHE3) inhibition with #4167 on ATP-induced alkalization. (a) Original experiment of perfused medullary thick ascending limb exposed to luminal #4167 (1 μm) and basolateral ATP (100 μm). (b) Summary (ΔpHi) of the series. *Indicates statistical significance P < 0.01, n = 8.
Mentions: A recent study from our group has established that furosemide causes an intracellular alkalization in the mTAL through increased apical NHE3-mediated H+ secretion (de Bruijn et al. 2013). To investigate whether the ATP-induced intracellular alkalization occurs by the same mechanism, basolateral ATP was tested in the presence of the specific NHE3 blocker #4167 (Reuter et al. 2008). Figure5a shows that luminal #4167 (1 μm) caused a significant intracellular acidification (ΔpH −0.35 ± 0.02, n = 8, Fig.5b). During this NHE3 inhibition, the ATP-induced alkalization was completely abolished in five of eight experiments, whereas in three experiments, the alkalization was strongly attenuated. These data indicate that apical NHE3 activity is required for the ATP-induced alkalization.

Bottom Line: The renal outer medullary K(+) channel (ROMK) is sensitive to intracellular pH where a reduction leads to closing of ROMK.We speculated that P2X receptor stimulation in the TAL could lead to changes in pHi , leading to a reduction in NaCl transport.Typically, Gq -coupled receptors cause a significant acidification of tubular epithelial cells, which was confirmed in this study, by P2Y2 and Ca(2+) sensing receptor stimulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus C, Denmark.

Show MeSH