Dendroaspis natriuretic peptide binds to the natriuretic peptide clearance receptor.
Dendroaspis natriuretic peptide (DNP) is a newly-described natriuretic peptide which lowers blood pressure via vasodilation. The natriuretic peptide clearance receptor (NPR-C) removes natriuretic peptides from the circulation, but whether DNP interacts with human NPR-C directly is unknown. The purpose of this study was to test the hypothesis that DNP binds to NPR-C. ANP, BNP, CNP, and the NPR-C ligands AP-811 and cANP(4-23) displaced [(125)I]-ANP from NPR-C with pM-to-nM K(i) values. DNP displaced [(125)I]-ANP from NPR-C with nM potency, which represents the first direct demonstration of binding of DNP to human NPR-C. DNP showed high pM affinity for the GC-A receptor and no affinity for GC-B (K(i)>1000 nM). DNP was 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.
Johns
Douglas G
DG
Vascular Biology and Thrombosis Department, Cardiovascular and Urogenital Center for Excellence in Drug Discovery, GlaxoSmithKline, King of Prussia, PA 19406, USA. Douglas.G.Johns@gsk.com
Ao
Zhaohui
Z
Heidrich
Bradley J
BJ
Hunsberger
Gerald E
GE
Graham
Taylor
T
Payne
Lisa
L
Elshourbagy
Nabil
N
Lu
Quinn
Q
Aiyar
Nambi
N
Douglas
Stephen A
SA
D000818:Animals; D004546:Elapid Venoms / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D045265:Natriuretic Peptides / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D011869:Radioligand Assay; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
C075597:Dendroaspis natriuretic peptide; D004546:Elapid Venoms; D036341:Intercellular Signaling Peptides and Proteins; D045265:Natriuretic Peptides; D010455:Peptides; D011994:Recombinant Proteins; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C