ArticleActa physiologica (Oxford, England)2015
P2X receptors trigger intracellular alkalization in isolated perfused mouse medullary thick ascending limb.
Article in Acta physiologica (Oxford, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 8 citations in OpenAlex.
- Selecting the right therapeutic target for kidney disease.Frontiers in pharmacology · 2022Review
- Extracellular Nucleotides and P2 Receptors in Renal Function.Physiological reviews · 2020Review
- Characterization of purinergic receptor expression in ARPKD cystic epithelia.Purinergic signalling · 2018Article
- P2X Receptors Inhibit NaCl Absorption in mTAL Independently of Nitric Oxide.Frontiers in physiology · 2017Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
aimsExtracellular ATP is an important regulator of renal tubular transport. Recently, we found that basolateral ATP markedly inhibits Na(+) and Cl(-) absorption in mouse medullary thick ascending limb (mTAL) via a P2X receptor. The underlying mechanism that mediates this ATP-dependent transport inhibition in mTAL is, however, unclear. 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.
methodsTo test this hypothesis, we measured pHi in single perfused mouse mTALs using the fluorescent ratiometric dye 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethylester.
resultsInterestingly, basolateral ATP (100 μm) caused a prominent, reversible intracellular alkalization of mTAL, with an average pHi increase of 0.14 ± 0.02 (n = 14). This was completely abolished by the P2X receptor antagonist periodate-oxidized ATP (50 μm). The P2X receptor-mediated intracellular alkalization required the activity of the apical Na(+) /H(+) exchanger (NHE3). 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.
conclusionThis study reports that stimulation of basolateral P2X receptors causes a substantial intracellular alkalization in the isolated perfused mouse mTAL. This intracellular alkalization is mediated through an increased apical NHE3 activity, similar to what we previously observed when tubular transport is inhibited with furosemide. This increased NHE3 activity causes H(+) secretion in the mTAL and provides further support that the TAL is a site of urinary acidification.
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