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Sodium-dependent regulation of renal amiloride-sensitive currents by apical P2 receptors.

Wildman, Scott S.P., Marks, Joanne, Turner, Clare M., Yew-Booth, Liang, Peppiatt-Wildman, Claire M., King, Brian F., Shirley, David G., Wang, WenHui, Unwin, Robert J. (2008) Sodium-dependent regulation of renal amiloride-sensitive currents by apical P2 receptors. Journal of the American Society of Nephrology, 19 (4). pp. 731-742. ISSN 1046-6673. E-ISSN 1533-3450. (doi:10.1681/ASN.2007040443) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided)

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Abstract

The epithelial sodium channel (ENaC) plays a major role in the regulation of sodium balance and BP by controlling Na(+) reabsorption along the renal distal tubule and collecting duct (CD). ENaC activity is affected by extracellular nucleotides acting on P2 receptors (P2R); however, there remain uncertainties over the P2R subtype(s) involved, the molecular mechanism(s) responsible, and their physiologic role. This study investigated the relationship between apical P2R and ENaC activity by assessing the effects of P2R agonists on amiloride-sensitive current in the rat CD. Using whole-cell patch clamp of principal cells of split-open CD from Na(+)-restricted rats, in combination with immunohistochemistry and real-time PCR, we found that activation of metabotropic P2R (most likely the P2Y(2) and/or (4) subtype), via phospholipase C, inhibited ENaC activity. In addition, activation of ionotropic P2R (most likely the P2X(4) and/or (4/6) subtype), via phosphatidylinositol-3 kinase, either inhibited or potentiated ENaC activity, depending on the extracellular Na(+) concentration; therefore, it is proposed that P2X(4) and/or (4/6) receptors might function as apical Na(+) sensors responsible for local regulation of ENaC activity in the CD and could thereby help to regulate Na(+) balance and systemic BP.

Item Type: Article
DOI/Identification number: 10.1681/ASN.2007040443
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Scott S.P. Wildman
Date Deposited: 10 Dec 2015 14:26 UTC
Last Modified: 29 May 2019 16:41 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/53052 (The current URI for this page, for reference purposes)
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