ArticleThe Journal of biological chemistry2008
Paracrine regulation of the epithelial Na+ channel in the mammalian collecting duct by purinergic P2Y2 receptor tone.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 132 citations in OpenAlex.
- Current understanding of ENaC regulation by P2Y2/PLC/PI(4,5)P2 pathway.Purinergic signalling · 2026Review
- P2YInternational journal of molecular sciences · 2025Review
- Epithelial NaComprehensive Physiology · 2024Review
- P2Y2 receptor decreases blood pressure by inhibiting ENaC.JCI insight · 2023Article
- Purinoceptor: a novel target for hypertension.Purinergic signalling · 2023Review
- Epac induces ryanodine receptor-dependent intracellular and inter-organellar calcium mobilization in mpkCCD cells.Frontiers in physiology · 2023Article
- PIPBiology · 2022Article
- Role for ovarian hormones in purinoceptor-dependent natriuresis.Biology of sex differences · 2020Article
- The Renal Physiology of Pendrin-Positive Intercalated Cells.Physiological reviews · 2020Review
- Diurnal Regulation of Renal Electrolyte Excretion: The Role of Paracrine Factors.Annual review of physiology · 2020Review
- Extracellular Nucleotides and P2 Receptors in Renal Function.Physiological reviews · 2020Review
- Lovastatin attenuates hypertension induced by renal tubule-specific knockout of ATP-binding cassette transporter A1, by inhibiting epithelial sodium channels.British journal of pharmacology · 2019Article
- Intercalated Cells of the Kidney Collecting Duct in Kidney Physiology.Seminars in nephrology · 2019Review
- Renal NaAmerican journal of physiology. Renal physiology · 2019Article
- New insights regarding epithelial Na+ channel regulation and its role in the kidney, immune system and vasculature.Current opinion in nephrology and hypertension · 2019Review
- Characterization of purinergic receptor expression in ARPKD cystic epithelia.Purinergic signalling · 2018Article
- The renal and blood pressure response to low sodium diet in P2X4 receptor knockout mice.Physiological reports · 2018Article
- Physiological mechanism of osmoregulatory adaptation in anguillid eels.Fish physiology and biochemistry · 2018Review
- Dietary salt blunts vasodilation by stimulating epithelial sodium channels in endothelial cells from salt-sensitive Dahl rats.British journal of pharmacology · 2018Article
- Renal intercalated cells and blood pressure regulation.Kidney research and clinical practice · 2017Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Growing evidence implicates a key role for extracellular nucleotides in cellular regulation, including of ion channels and renal function, but the mechanisms for such actions are inadequately defined. We investigated purinergic regulation of the epithelial Na+ channel (ENaC) in mammalian collecting duct. We find that ATP decreases ENaC activity in both mouse and rat collecting duct principal cells. ATP and other nucleotides, including UTP, decrease ENaC activity via apical P2Y2 receptors. ENaC in collecting ducts isolated from mice lacking this receptor have blunted responses to ATP. P2Y2 couples to ENaC via PLC; direct activation of PLC mimics ATP action. Tonic regulation of ENaC in the collecting duct occurs via locally released ATP; scavenging endogenous ATP and inhibiting P2 receptors, in the absence of other stimuli, rapidly increases ENaC activity. Moreover, ENaC has greater resting activity in collecting ducts from P2Y2-/- mice. Loss of collecting duct P2Y2 receptors in the knock-out mouse is the primary defect leading to increased ENaC activity based on the ability of direct PLC stimulation to decrease ENaC activity in collecting ducts from P2Y2-/- mice in a manner similar to ATP in collecting ducts from wild-type mice. These findings demonstrate that locally released ATP acts in an autocrine/paracrine manner to tonically regulate ENaC in mammalian collecting duct. Loss of this intrinsic regulation leads to ENaC hyperactivity and contributes to hypertension that occurs in P2Y2 receptor-/- mice. P2Y2 receptor activation by nucleotides thus provides physiologically important regulation of ENaC and electrolyte handling in mammalian kidney.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.