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Author Notes:

Address for reprint requests and other correspondence: H.-F. Bao, Dept. of Physiology, Emory Univ. School of Medicine, Atlanta, GA 30322 (e-mail: hbao2@emory.edu).

L.-J. Guo and A. A. Alli contributed equally to this work.

Present address of L.-J. Guo: SHOU-Gang Hospital, Peking University, Shi-Jing Shan District, Beijing, China.

Author contributions: L.-J.G., A.A.A., and H.-F.B. performed experiments; L.-J.G., A.A.A., D.C.E., and H.-F.B. analyzed data; L.-J.G., A.A.A., D.C.E., and H.-F.B. approved final version of manuscript; A.A.A., D.C.E., and H.-F.B. conception and design of research; A.A.A., D.C.E., and H.-F.B. interpreted results of experiments; A.A.A., D.C.E., and H.-F.B. prepared figures; A.A.A. drafted manuscript; A.A.A., D.C.E., and H.-F.B. edited and revised manuscript.

We thank B. J. Duke for maintaining 2F3 cells in culture.

No conflicts of interest, financial or otherwise, are declared by the author(s).

Subjects:

Keywords:

  • atrial natriuretic peptide
  • ENaC
  • nitric oxide
  • cGMP
  • PKG

ENaC is regulated by natriuretic peptide receptor-dependent cGMP signaling

Tools:

Journal Title:

AJP - Renal Physiology

Volume:

Volume 304, Number 7

Publisher:

, Pages F930-F937

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Epithelial sodium channels (ENaCs) located at the apical membrane of polarized epithelial cells are regulated by the second messenger guanosine 3′,5′-cyclic monophosphate (cGMP). The mechanism for this regulation has not been completely characterized. Guanylyl cyclases synthesize cGMP in response to various intracellular and extracellular signals. We investigated the regulation of ENaC activity by natriuretic peptide-dependent activation of guanylyl cyclases in Xenopus 2F3 cells. Confocal microscopy studies show natriuretic peptide receptors (NPRs), including those coupled to guanylyl cyclases, are expressed at the apical membrane of 2F3 cells. Single-channel patch-clamp studies using 2F3 cells revealed that atrial natriuretic peptide (ANP) or 8-(4-chlorophenylthio)-cGMP, but not C-type natriuretic peptide or cANP, decreased the open probability of ENaC. This suggests that NPR-A, but not NPR-B or NPR-C, is involved in the natriuretic peptide-mediated regulation of ENaC activity. Also, it is likely that a signaling pathway involving cGMP and nitric oxide (NO) are involved in this mechanism, since inhibitors of soluble guanylyl cyclase, protein kinase G, inducible NO synthase, or an NO scavenger blocked or reduced the effect of ANP on ENaC activity.

Copyright information:

© 2013 the American Physiological Society

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