Novel snake venom ligand dendroaspis natriuretic peptide is selective for natriuretic peptide receptor-A in human heart: downregulation of natriuretic peptide receptor-A in heart failure.

Abstract

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 [125I]-DNP and used this to localize high-affinity (K(D)=0.2 nmol/L), saturable, specific binding sites in adult human heart (n=6) and coronary artery (n=8). In competition binding experiments, atrial natriuretic peptide and brain type natriuretic peptide had greater affinity for [125I]-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 [125I]-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.

• Authors: Gurminder Singh, Rhoda E Kuc, Janet J Maguire, Mark Fidock, Anthony P Davenport
• Journal: Circulation research (Circ Res) Vol. 99 Issue 2 Pg. 183-90 (Jul 21 2006) ISSN: 1524-4571 [Electronic] United States
• PMID: 16778132 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dendroaspis natriuretic peptide
• Elapid Venoms
• Intercellular Signaling Peptides and Proteins
• Iodine Radioisotopes
• Ligands
• Peptides
• RNA, Messenger
• Snake Venoms
• Guanylate Cyclase
• Receptors, Atrial Natriuretic Factor
• atrial natriuretic factor receptor A

Topics

• Adult
• Binding Sites
• Coronary Vessels (chemistry, metabolism)
• Down-Regulation (genetics)
• Elapid Venoms (pharmacokinetics)
• Female
• Guanylate Cyclase (genetics, metabolism)
• Heart Failure
• Heart Ventricles (chemistry)
• Humans
• Immunohistochemistry
• Intercellular Signaling Peptides and Proteins
• Iodine Radioisotopes (pharmacokinetics)
• Ligands
• Male
• Middle Aged
• Myocardium (metabolism)
• Peptides (pharmacokinetics)
• Protein Binding
• RNA, Messenger (analysis)
• Receptors, Atrial Natriuretic Factor (genetics, metabolism)
• Snake Venoms