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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.This increased NHE3 activity causes H(+) secretion in the mTAL and provides further support that the TAL is a site of urinary acidification.

View Article: PubMed Central - PubMed

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

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Model of P2X receptor-mediated intracellular alkalization in medullary thick ascending limb. Stimulation of the P2X receptor causes an influx of cations, which should lead to cell swelling. This in turn may stimulate the apical Na+/H+ exchanger (NHE3), leading to the observed intracellular alkalization.
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fig07: Model of P2X receptor-mediated intracellular alkalization in medullary thick ascending limb. Stimulation of the P2X receptor causes an influx of cations, which should lead to cell swelling. This in turn may stimulate the apical Na+/H+ exchanger (NHE3), leading to the observed intracellular alkalization.

Mentions: Basolaterally applied ATP is established to inhibit Na+ and Cl− absorption substantially (approx. 25%) via P2X receptors (Marques et al. 2012). The current results indicate that inhibition of transport, irrespective of the mode of induction, associates with an intracellular alkalization caused by increased H+ secretion. Taken together, these results indicate that ATP, much similar to furosemide, increases the driving force for luminal H+ exit via the NHE3 (Fig.7 for model). It is worth to note that partial transport inhibition as seen under P2X receptor stimulation causes a moderate alkalization as compared to a massive pH effect when Na+ and Cl− absorption was fully inhibited with furosemide. These results indicate that the rate of Na+ and Cl− absorption inversely correlates with the rate of H+ secretion via apical NHE3. Indeed, it has been shown that AVP, which stimulates NKCC2 activity (Welker et al. 2008, Marques et al. 2013), reduces reabsorption, consistent with a decrease in NHE3 activity (Good 1990).


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)

Model of P2X receptor-mediated intracellular alkalization in medullary thick ascending limb. Stimulation of the P2X receptor causes an influx of cations, which should lead to cell swelling. This in turn may stimulate the apical Na+/H+ exchanger (NHE3), leading to the observed intracellular alkalization.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig07: Model of P2X receptor-mediated intracellular alkalization in medullary thick ascending limb. Stimulation of the P2X receptor causes an influx of cations, which should lead to cell swelling. This in turn may stimulate the apical Na+/H+ exchanger (NHE3), leading to the observed intracellular alkalization.
Mentions: Basolaterally applied ATP is established to inhibit Na+ and Cl− absorption substantially (approx. 25%) via P2X receptors (Marques et al. 2012). The current results indicate that inhibition of transport, irrespective of the mode of induction, associates with an intracellular alkalization caused by increased H+ secretion. Taken together, these results indicate that ATP, much similar to furosemide, increases the driving force for luminal H+ exit via the NHE3 (Fig.7 for model). It is worth to note that partial transport inhibition as seen under P2X receptor stimulation causes a moderate alkalization as compared to a massive pH effect when Na+ and Cl− absorption was fully inhibited with furosemide. These results indicate that the rate of Na+ and Cl− absorption inversely correlates with the rate of H+ secretion via apical NHE3. Indeed, it has been shown that AVP, which stimulates NKCC2 activity (Welker et al. 2008, Marques et al. 2013), reduces reabsorption, consistent with a decrease in NHE3 activity (Good 1990).

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.This increased NHE3 activity causes H(+) secretion in the mTAL and provides further support that the TAL is a site of urinary acidification.

View Article: PubMed Central - PubMed

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

Show MeSH
Related in: MedlinePlus