title: ANP-induced signaling cascade and its implications in renal pathophysiology.
abstract: The balance between vasoconstrictor/sodium-retaining and vasodilator/natriuretic systems is essential for maintaining body fluid and electrolyte homeostasis. Natriuretic peptides, such as atrial natriuretic peptide (ANP), belong to the vasodilator/natriuretic system. ANP is produced by the conversion of pro-ANP into ANP, which is achieved by a proteolytical cleavage executed by corin. In the kidney, ANP binds to the natriuretic peptide receptor-A (NPR-A) and enhances its guanylyl cyclase activity, thereby increasing intracellular cyclic guanosine monophosphate production to promote natriuretic and renoprotective responses. In the glomerulus, ANP increases glomerular permeability and filtration rate and antagonizes the deleterious effects of the renin-angiotensin-aldosterone system activation. Along the nephron, natriuretic and diuretic actions of ANP are mediated by inhibiting the basolaterally expressed Na(+)-K(+)-ATPase, reducing apical sodium, potassium, and protein organic cation transporter in the proximal tubule, and decreasing Na(+)-K(+)-2Cl(-) cotransporter activity and renal concentration efficiency in the thick ascending limb. In the medullary collecting duct, ANP reduces sodium reabsorption by inhibiting the cyclic nucleotide-gated cation channels, the epithelial sodium channel, and the heteromeric channel transient receptor potential-vanilloid 4 and -polycystin 2 and diminishes vasopressin-induced water reabsorption. Long-term ANP treatment may lead to NPR-A desensitization and ANP resistance, resulting in augmented sodium and water reabsorption. In mice, corin deficiency impairs sodium excretion and causes salt-sensitive hypertension. Characteristics of ANP resistance and corin deficiency are also encountered in patients with edema-associated diseases, highlighting the importance of ANP signaling in salt-water balance and renal pathophysiology.
authors: Institute of Anatomy, Department of Medicine, University of Fribourg, Fribourg, Switzerland; and franziska.theilig@unifr.ch.
authors: Franziska
authors: F
authors: Theilig
authors: Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Ohio.
authors: Qingyu
authors: Q
authors: Wu
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000502:physiology*; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D051379:Mice; D023421:Models, Animal; D012697:Serine Endopeptidases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014882:Water-Electrolyte Balance / Q000502:physiology
chemical_list: D009320:Atrial Natriuretic Factor; C119812:CORIN protein, human; C485617:Corin protein, mouse; D012697:Serine Endopeptidases
keywords: ANP; corin; edema; volume retention
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