title: ENaC is regulated by natriuretic peptide receptor-dependent cGMP signaling.
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.
authors: Department of Physiology, Emory University School of Medicine and the Center for Cell and Molecular Signaling, Atlanta, GA 30322, USA.
authors: Lai-Jing
authors: LJ
authors: Guo
authors: Abdel A
authors: AA
authors: Alli
authors: Douglas C
authors: DC
authors: Eaton
authors: Hui-Fang
authors: HF
authors: Bao
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology / Q000502:physiology*; D002460:Cell Line; D006152:Cyclic GMP / Q000378:metabolism / Q000502:physiology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000187:drug effects / Q000502:physiology*; D006162:Guanylate Cyclase / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D051379:Mice; D020098:Natriuretic Peptide, C-Type / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D050705:Receptors, Guanylate Cyclase-Coupled / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D000071756:Soluble Guanylyl Cyclase; D014982:Xenopus laevis
chemical_list: D053503:Epithelial Sodium Channels; D018160:Receptors, Cytoplasmic and Nuclear; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D050705:Receptors, Guanylate Cyclase-Coupled; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP