Dendroaspis natriuretic peptide is degraded by a metalloproteinase in the rat kidney

Abstract

Abstract. Our previous study demonstrated that the concentration of dendroaspis natriuretic peptide (DNP) was markedly higher than that of atrial NP (ANP) in rabbit plasma, indicating that DNP has a different metabolic rate from other NPs. Therefore, the metabolic characteristics of DNP in mammals require further analysis. The stabilities of NPs were determined by incubating 125 I-labeled ANP, brain NP (BNP), C-type NP (CNP) and DNP at 37˚C for 1, 2 and 4 h, and analyzing their profiles by reversed-phase high-performance liquid chromatography.125 I-labeled ANP, BNP and CNP were quickly degraded in rat plasma, while 125 I-labeled DNP was stable for 4 h. The relative stability of the peptides following incubation in rat plasma followed the rank order of: DNP>>>ANP≥BNP>>CNP. Organs were also examined for the degradation of DNP, including the spleen, kidney, liver, heart and lung. The physiological target organ for the degradation of DNP was observed to be the kidney. Furthermore, degradation of DNP in the kidney was attenuated by phenanthroline, a metalloproteinase inhibitor. Therefore, these results indicate that DNP has a longer stability in plasma and that it may have strong therapeutic applications in cardiac disease.

Characteristics of dendroaspis natriuretic peptide and its receptor in streptozotocin-induced diabetic rats

“…The natriuretic peptide receptors (NPRs) for DNP have been reported to localize to the smooth muscle tissue of the human mammary artery (4); in addition, DNP has been observed to induce vasodilatation via the direct activation of these receptors (7). Our previous studies provided evidence that DNP exerts renal actions via the NPR-A subtype and demonstrated that DNP and its specific receptor are present in the kidneys of rabbits (8)(9)(10). Collectively, these results suggested that DNP has a physiological role in regulating the renal function of mammals by interacting with specific NPRs, which have a particular guanylyl cyclase (pGC) domain.…”