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Purinergic regulation of ENaC in rat and mouse collecting duct
Author(s) -
Bugaj Vladislav,
Pochynyuk Oleh,
Stockand James D
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1215.1
Subject(s) - purinergic receptor , purinergic signalling , epithelial sodium channel , microbiology and biotechnology , reabsorption , p2y receptor , suramin , medicine , chemistry , endocrinology , receptor , biology , extracellular , agonist , kidney , adenosine receptor , sodium , organic chemistry
The epithelial sodium channel (ENaC) plays a critical role in setting systemic salt and water balance and thus, blood pressure. Activity of this channel is limitingfor Na + reabsorption at the renal collecting duct. Cell signaling in response to purinergic stimulation decreases ENaC activity in models of polarized collecting duct epithelia. Moreover, targeted deletion of purinergic P2Y receptors causes hypertension in mice associated with dysfunctional salt handling at the collecting duct. Thus, we test here the hypothesis that the purinergic agonist, ATP, modulates the activity of ENaC in isolated, split‐open mouse and rat collecting ducts. In addition, we define the cellular signaling pathway underpinning such regulation. We find that ATP rapidly decreases ENaCopen probability in both the mouse and rat collecting duct. Dwell time analysis reveals that ATP forces ENaC toward a closed state. Inhibiting purinergic signaling withsuramin blocks the actions of ATP and rescues ENaC activity. The PLC inhibitor, U73122, recapitulates the actionof suramin. We conclude that ATP through metabotropic purinergic receptors coupled to PLC decreases ENaC activity by rapidly decreasing channel open probability. It is likely that PLC‐mediated reduction in apical membrane PI(4,5)P 2 levels couples purinergic signaling to decreases in channel open probability in native collecting ducts. These results suggest that purinergic signaling is a major regulator of ENaC activity in renal epithelialcells.