Role of natriuretic peptides in ion transport mechanisms

Abstract

Natriuretic peptides (NP) act as ligands on the guanylyl cyclase family of receptors. The NP binding site on these receptors is extracellular and the guanylyl cyclase and protein kinase domains are intracellular. The guanylyl cyclase receptor catalyzes the synthesis of the second messenger molecule, cGMP, which activates protein kinase. This in turn is involved in the phosphorylation of various ion transport proteins. Ion transport proteins, which are modulated by NP and are thought to underlie the natriuretic and diuretic actions of NP, include: (a) calcium‐activated K+ channels; (b) ATP‐sensitive K+ channels; (c) inwardly‐rectifying K+ channels; (d) outwardly‐rectifying K+ channels; (e) L‐type Ca²+ channels; (f) Cl‐ channels including cystic fibrosis transmembrane conductance regulator Cl‐ channels; (g) Na+‐ K+ 2Cl‐ co‐transporter; (h) Na+‐ K+ ATPase; (i) Na+ channels; (j) stretch‐activated channels; and (k) water channels. It appears that NP modulate the kinetics, rather than the conductance, of ion channels. Some of these channels, like the Ca²+, ATP‐sensitive K+ and stretch‐activated channels, are also involved in NP secretion. In addition, the structural properties of the NP, e.g., ovCNP‐22 and ovCNP‐39, appear to confer on them the ability to form ion channels. These CNP‐formed ion channels can modify the trans‐membrane signal transduction and second messenger systems underlying NP‐induced pathological effects. © 1999 John Wiley & Sons, Inc. Med Res Rev, 19, No. 1, 75–94, 1999.

Modulation by Brain Natriuretic Peptide of GABA Receptors on Rat Retinal ON-Type Bipolar Cells

“…Natriuretic peptides (NPs) constitute a family of three structurally related hormones: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and the C-type natriuretic peptide (CNP), which are encoded by three different genes and share a 17 amino acid internal ring (Kourie and Rive, 1999). There are three types of receptors for these peptides (NPRs) (Nakao et al, 1992).…”

“…Two of these, types A and B (NPR-A and NPR-B), are both single transmembrane-spanning proteins containing particle guanylyl cyclase (pGC) activity in their intracellular domain. Activation of these receptors stimulates the production of the intracellular second messenger cGMP and thereby activates cGMP-binding proteins, such as cGMP-dependent protein kinase G (PKG) (Kourie and Rive, 1999). ANP and, to a lesser extent, BNP activate NPR-A, whereas CNP preferentially activates NPR-B.…”

Inhibition of NHE-1 Na+/H+ exchanger by natriuretic peptides in ocular nonpigmented ciliary epithelium

“…The NP binding of NPR-A and NPR-B causes the generation of intracellular cGMP that leads to the activation of a protein kinase G (PKG). Downstream kinase activities include regulation of ion channels, substrate protein phosphorylation, and cellular proliferation (26).…”

Mechanisms of hepatocyte protection against hypoxic injury by atrial natriuretic peptide

“…1 Like other NPs, ANP is produced in response to stress conditions such as cardiac hypoxia and atrial stretch and has potent vasodilating, hypotensive, and natriuretic activities. 2,3 In addition, evidence indicates that ANP modulates cell proliferation and cardiomyocyte hypertrophy 4 and exerts cytoprotective functions. Indeed, ANP has been shown to efficiently reduce kidney damage by both warm and cold hypoxia 5,6 to prevent reperfusion injury in perfused hearts.…”