title: Chimeric natriuretic peptide ACNP stimulates both natriuretic peptide receptors, the NPRA and NPRB.
abstract: Here, we investigated the receptor profile of the newly designed natriuretic peptide (NP) ACNP consisting of the N- and C-terminus of human ANP and the ring structure of CNP, its potency/efficacy in stimulating cGMP generation in primary cells, and its stability towards peptidase activity. ACNP stimulated both human natriuretic peptide receptors (NPRs), NPRA and NPRB, as potent as their native ligands in receptor transfected cells. Consequently, ACNP was more efficient in generating cGMP compared to ANP, BNP, and CNP, in primary cells expressing both NPRs. All NPs have been similarly degraded by neprilysin, except the neprilysin-resistant BNP. However, ACNP was fastest degraded in serum, while CNP was most stable. Congruently, CNP but not ACNP reduced blood pressure most significantly after acute peptide infusion in normotensive mice. Our data identify ACNP as the first compound being able to stimulate both natriuretic receptors with similar potency and efficacy as their respective ligands.
authors.affiliation: Centre for Cardiovascular and Metabolic Research, Hull York Medical School, University of Hull, Hull HU6 7RX, UK.
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhu
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Anja
authors.initials: A
authors.lastname: Schwiebs
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019556:COS Cells; D002522:Chlorocebus aethiops; D006152:Cyclic GMP / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D045265:Natriuretic Peptides / Q000494:pharmacology*; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology*; D000099242:Atrial Natriuretic Factor Receptor B
chemical_list: D006152:Cyclic GMP; D045265:Natriuretic Peptides; D017461:Receptors, Atrial Natriuretic Factor; D011994:Recombinant Proteins; D000099242:Atrial Natriuretic Factor Receptor B; C091715:atrial natriuretic factor receptor A