P2X receptors trigger intracellular alkalization in isolated perfused mouse medullary thick ascending limb.
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.
Affiliation: Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus C, Denmark.Show MeSH
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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).
Affiliation: Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus C, Denmark.