Atrial Natriuretic Peptides (ANP/ANF) and Related Peptides

Definition
Atrial natriuretic peptide (ANP), atrial natriuretic factor (ANF), or atriopeptin, is a hormone secreted by heart muscle cells. It is involved in the homeostatic control of body water, sodium, potassium and fat. It is released by muscle cells in the upper chambers (atria) of the heart (atrial myocytes), in response to high blood pressure. It is closely related to brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP).

Discovery
ANP was discovered in 1981 by a team in Ottawa led by Adolfo J. de Bold after they made the seminal observation that injection of atrial tissue extracts into rats caused copious natriuresis1.

Structural characteristics
ANP is a 28-amino acid peptide with a 17-amino acid ring in the middle of the molecule. The ring is formed by a disulfide bond between two cysteine residues at positions 7 and 23. BNP and CNP also share the same amino acid ring. The ANP receptor occurs as a dimer of a single span transmembrane polypeptide, each containing an extracellular hormone-binding domain and an intracellular domain consisting of a protein kinase-like, ATP-dependent regulatory domain and a GC catalytic domain2.

Mode of action
The activities of ANP are mediated by the ANP receptor or the A-type natriuretic peptide receptor carrying intrinsic guanylate cyclase (GC) catalytic activity. Binding of the hormone to the receptor stimulates GC catalytic activity, thereby elevating intracellular cGMP levels. cGMP in turn, mediates the hormonal actions through cGMP-regulated ion channels, protein kinases and phosphodiesterases.

Functions
ANP stimulates vasodilatation, fluid egress, increases glomerular filtration and salt and water excretion. It also blocks the release and actions of several hormones, including angiotensin II, aldosterone and vasopressin. ANP levels are commonly elevated when there is excessive fluid volume or hypertension, and the hormone may be important in combating these states. It shows promise as an agent to treat heart failure, renal failure and fluid excess states3.

References
1.Mebazaa A and Payen D (1990). Atrial natriuretic factor. Ann Fr Anesth Reanim., 9(2):153-168.

2.Ogawa H, Qiu Y, Ogata CM, Misono KS (2004). Crystal structure of hormone-bound atrial natriuretic peptide receptor extracellular domain: rotation mechanism for transmembrane signal transduction. J Biol Chem., 279(27):28625-28631.

3.Baxter JD, Lewicki JA, Gardner DG (1988). Atrial Natriuretic Peptide. Nature BioTechnology, 6: 529 – 546.