Novel Snake Venom Ligand Dendroaspis Natriuretic Peptide Is Selective for Natriuretic Peptide Receptor-A in Human Heart

Gurminder Singh, Rhoda E. Kuc, Janet J. Maguire, Mark Fidock, Anthony P. Davenport
2006 Circulation Research  
The natriuretic peptides are considered to be cardioprotective; however, their receptors have not been identified in human myocardium using radiolabeled analogs. Dendroaspis natriuretic peptide (DNP) has been recently identified as a new member of this peptide family and is thought to be less susceptible to enzymatic degradation. Therefore, we have developed the novel radiolabeled analog [ 125 I]-DNP and used this to localize high-affinity (K D ϭ0.2 nmol/L), saturable, specific binding sites in
more » ... adult human heart (nϭ6) and coronary artery (nϭ8). In competition binding experiments, atrial natriuretic peptide and brain type natriuretic peptide had greater affinity for [ 125 I]-DNP binding sites than C-type natriuretic peptide and the natriuretic peptide receptor (NPR)-C ligand, cANF. This rank order of potency suggested binding of [ 125 I]-DNP was specific to NPR-A. Messenger RNA encoding NPR-A was identified in left ventricle and coronary artery smooth muscle, and expression was confirmed by immunocytochemical studies at the protein level. In addition, fluorescence dual labeling immunocytochemistry localized NPR-A protein to cardiomyocytes, endocardial endothelial cells, and smooth muscle of intramyocardial vessels. Importantly, we demonstrated a significant downregulation in the density of NPR-A in heart and coronary artery of patients with ischemic heart disease that may explain, in part, the attenuated natriuretic peptide response reported in this patient group. (Circ Res. 2006;99:183-190.)
doi:10.1161/01.res.0000232322.06633.d3 pmid:16778132 fatcat:vfaba7snkjhmtgxndhyyzcbevy