Dietary Na+ inhibits the open probability of the epithelial sodium channel in the kidney by enhancing apical P2Y2-receptor tone

Oleh Pochynyuk, Timo Rieg, Vladislav Bugaj, Jana Schroth, Alla Fridman, Gerry R. Boss, Paul A. Insel, James D Stockand, Volker Vallon

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Apical release of ATP and UTP can activate P2Y2 receptors in the aldosterone-sensitive distal nephron (ASDN) and inhibit the open probability (Po) of the epithelial sodium channel (ENaC). Little is known, however, about the regulation and physiological relevance of this system. Patch-clamp studies in freshly isolated ASDN provide evidence that increased dietary Na+ intake in wild-type mice lowers ENaC Po, consistent with a contribution to Na+ homeostasis, and is associated with increased urinary concentrations of UTP and the ATP hydrolytic product, ADP. Genetic deletion of P2Y2 receptors in mice (P2Y2 -/-; littermates to wild-type mice) or inhibition of apical P2Y-receptor activation in wild-type mice prevents dietary Na +-induced lowering of ENaC Po. Although they lack suppression of ENaC Po by dietary NaCl, P2Y2 -/- mice do not exhibit NaCl-sensitive blood pressure, perhaps as a consequence of compensatory down-regulation of aldosterone levels. Consistent with this hypothesis, clamping mineralocorticoid activity at high levels unmasks greater ENaC activity and NaCl sensitivity of blood pressure in P2Y2 -/- mice. The studies indicate a key role of the apical ATP/UTP-P2Y2-receptor system in the inhibition of ENaC Po in the ASDN in response to an increase in Na+ intake, thereby contributing to NaCl homeostasis and blood pressure regulation.

Original languageEnglish (US)
Pages (from-to)2056-2065
Number of pages10
JournalFASEB Journal
Volume24
Issue number6
DOIs
StatePublished - Jun 2010

Fingerprint

Purinergic P2Y2 Receptors
Epithelial Sodium Channels
Aldosterone
Uridine Triphosphate
Blood pressure
Kidney
Nephrons
Adenosine Triphosphate
Blood Pressure
Pressure regulation
Homeostasis
Mineralocorticoids
Clamping devices
Adenosine Diphosphate
Constriction
Chemical activation
Down-Regulation

Keywords

  • Aldosterone
  • ATP
  • Blood pressure
  • Distal nephron
  • Nucleotide receptors

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Pochynyuk, O., Rieg, T., Bugaj, V., Schroth, J., Fridman, A., Boss, G. R., ... Vallon, V. (2010). Dietary Na+ inhibits the open probability of the epithelial sodium channel in the kidney by enhancing apical P2Y2-receptor tone. FASEB Journal, 24(6), 2056-2065. https://doi.org/10.1096/fj.09-151506

Dietary Na+ inhibits the open probability of the epithelial sodium channel in the kidney by enhancing apical P2Y2-receptor tone. / Pochynyuk, Oleh; Rieg, Timo; Bugaj, Vladislav; Schroth, Jana; Fridman, Alla; Boss, Gerry R.; Insel, Paul A.; Stockand, James D; Vallon, Volker.

In: FASEB Journal, Vol. 24, No. 6, 06.2010, p. 2056-2065.

Research output: Contribution to journalArticle

Pochynyuk, O, Rieg, T, Bugaj, V, Schroth, J, Fridman, A, Boss, GR, Insel, PA, Stockand, JD & Vallon, V 2010, 'Dietary Na+ inhibits the open probability of the epithelial sodium channel in the kidney by enhancing apical P2Y2-receptor tone', FASEB Journal, vol. 24, no. 6, pp. 2056-2065. https://doi.org/10.1096/fj.09-151506
Pochynyuk, Oleh ; Rieg, Timo ; Bugaj, Vladislav ; Schroth, Jana ; Fridman, Alla ; Boss, Gerry R. ; Insel, Paul A. ; Stockand, James D ; Vallon, Volker. / Dietary Na+ inhibits the open probability of the epithelial sodium channel in the kidney by enhancing apical P2Y2-receptor tone. In: FASEB Journal. 2010 ; Vol. 24, No. 6. pp. 2056-2065.
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