Dendroaspis Natriuretic Peptides

Definition
Dendroaspis natriuretic peptide (DNP), isolated from the venom of the green Mamba snake Dendroaspis angusticeps, is a natriuretic peptide which lowers blood pressure via vasodilation and is resistant to breakdown by neutral endopeptidases 1.

Related peptides
DNP contains a disulfide ring structure similar to that of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). DNP-like immunoreactivity (DNP-LI) was reported to be present in human plasma and atrial myocardium and to be elevated in human congestive heart failure 2.

Discovery
DNP was discovered in the venom of green mamba by Schweitz et al., in 1992 3.

Structural Characteristics
DNP is a 38 amino acid peptide containing a 17 amino acid disulfide ring structure similar to that of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) and a 15-residue C terminal extension 2.

Mode of Action
DNP may function through the NPR-A receptor, which is linked to a particulate guanylyl cyclase and cGMP generation and is also highly expressed in inner medullary collecting duct cells. This conclusion is also supported by the report that DNP displaces ANP binding in vascular smooth muscle cells. This peptide potently vasorelaxes isolated rodent aorta and canine coronary arteries with comparable potency to ANP 2. DNP significantly inhibits gastric motility in the gastric antrum of guinea pigs. The inhibitory effect occurs via a cGMP-dependent pathway, and a calcium-activated potassium channel is also thought to be involved in the relaxation induced by DNP 4.

Functions
DNP was found to be nearly 10-fold more potent than ANP at stimulating cGMP production in GC-A expressing cells. Blockade of NPR-C might represent a novel therapeutic approach in augmenting the known beneficial actions of DNP in cardiovascular diseases such as hypertension and heart failure 1. DNP may play a physiological role in the regulation of sodium excretion 2.

References
1. Johns DG, Ao Z, Heidrich BJ, Hunsberger GE, Graham T, Payne L, Elshourbagy N, Lu Q, Aiyar N, Douglas SA (2007). Dendroaspis natriuretic peptide binds to the natriuretic peptide clearance receptor. Biochem Biophys Res Commun., 358(1)145-149.
2. Lisy O, Jougasaki M, Heublein DM, Schirger JA, Chen HH, Wennberg PW, Burnett JC (1999). Renal actions of synthetic Dendroaspis natriuretic peptide. Kidney International, 56(2):502–508.
3. Schweitz H, Vigne P, Moinier D, Frelin C, Lazdunski M (1992). A new member of the natriuretic peptide family is present in the venom of the green mamba (Dendroaspis angusticeps) J. Biol. Chem., 267(20):13928-13932.
4. Guo HS, Cai ZX, Wu TH, Xu J, Qiu Y, Xu WX (2007). Inhibitory effect of dendroaspis natriuretic peptide on spontaneous contraction in gastric antral circular smooth muscles of guinea pigs. Acta Pharmacol Sin., 28(11):797–1802.