Atrial natriuretic peptide guanylyl cyclase binding

Natriuretic peptides are a family of peptide hormones. All of them contain a 17-amino acid long ring that is closed by a disulfide bond between two cysteine residues. ANP (atrial natriuretic peptide) is mainly expressed in the atria of the heart, whereas BNP (B-type natriuretic peptide) is synthesized in the ventricular myocardium. CNP occurs mainly in the endothelium and is thought to have a paracrine function. ANF and BNF lower blood pressure by a direct effect on smooth muscle and on the salt retention in the kidney. Natriuretic peptides bind and activate particulate guanylyl cyclases. 

For the receptors that bind atrial natriuretic peptides and the peptides guanylin and uroguanylin, the intracellular domain is not a protein kinase but rather a guanylyl cyclase that synthesizes the second messenger cyclic guanosine monophosphate (cyclic GMP), which activates a cyclic GMP-dependent protein kinase (PKG) and can modulate the activities of several cyclic nucleotide phosphodiesterases, among other effectors. 

Some receptors appear to be linked to the stimulation of guanylyl-cyclase. These membrane receptors mediate the action of the atrial natriuretic peptide (ANP), the heat-stable enterotoxin of E. coli and the receptors involved in fertilization in some species. These membrane receptors are glycoproteins of about 130-160 kDa spanning the membrane only once. The binding of the peptides occurs at the extracellular domain, while the intracellular regions contain both cyclase catalytic domains, converting GTP to cGMP, and a protein kinase-like domain. 

Cyclic GMP is made from GTP by the enzyme gua-nylyl cyclase, which exists in soluble and membrane-bound forms. Each of these isozymes has unique physiologic properties. The atriopeptins, a family of peptides produced in cardiac atrial tissues, cause natriuresis, diuresis, vasodilation, and inhibition of aldosterone secretion. These peptides (eg, atrial natriuretic factor) bind to and activate the membrane-bound form of guanylyl cyclase. This results in an increase of cGMP by as much as 50-fold in some cases, and this is thought to mediate the effects mentioned above. Other evidence links cGMP to vasodilation. A series of compounds, including nitroprusside, nitroglycerin, nitric oxide, sodium nitrite, and sodium azide, all cause smooth muscle re-... 

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