Skip to main content

Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Volume 14 Supplement 1

6th International Conference on cGMP: Generators, Effectors and Therapeutic Implications

Krait natriuretic peptide (KNP): a non-classical NP

BMC Pharmacology and Toxicology volume 14, Article number: P67 (2013) Cite this article

  • 1083 Accesses

Background

Cardiac homeostasis is a complex phenomenon, which is maintained by the interplay of factors that up and down regulate blood pressure. Natriuretic peptides (NPs), which cause vasodilation and increased water-electrolyte excretion, are among the most vital hormonal controls of blood pressure. NPs elicit their function by binding to membrane bound guanylyl cyclase receptor. Three mammalian NPs are known, namely ANP, BNP and CNP, which are structurally similar with a 17 residue ring and a short (5-6 residues) C-terminal tail.

Results

Here, we describe the characterization of a novel NP from krait venom (KNP). In contrast to mammalian NPs, KNP has an extensively long 38 residue C-terminal tail, which has propensity to form α-helix, unlike other elapid NPs. The ex-vivo organ bath studies showed that the ability of KNP to relax the pre-contracted aortic strip was weaker than ANP, and it does so via a different mechanism. It arbitrates vasodilation via endothelium-dependent pathways in contrast to ANP which mediates via endothelium-independent mechanisms. Putative helical segment showed an equipotent vasorelaxation in an endothelium-dependent manner, while only the ring of KNP showed similar vasorelaxation as ANP in an endothelium-independent manner. Deletion of the C-terminal helical segment abrogates KNP’s activity suggesting its definitive role in vasorelaxation. Further with different inhibitors, we have delineated the necessity for nitric oxide, prostacyclin and endothelium derived hyperpolarization factor (EDHF) for KNP mediated vasodilation.

Conclusion

We have established that KNP mediates vasodilation by a unique mechanism that can be attributed to its C-terminal tail.

Author information

Affiliations

  1. Department of Biological Sciences, National University of Singapore, Singapore
    • Sindhuja Sridharan
    •  & R Manjunatha Kini
  2. Department of Biochemistry and Molecular Biophysics, Virginia Commonwealth University, Richmond, VA, 23298, USA
    • R Manjunatha Kini
  3. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia
    • R Manjunatha Kini
Authors
  1. Search for Sindhuja Sridharan in:
  2. Search for R Manjunatha Kini in:

Corresponding author

Correspondence to Sindhuja Sridharan.

Rights and permissions

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Cite this article

Sridharan, S., Kini, R.M. Krait natriuretic peptide (KNP): a non-classical NP. BMC Pharmacol Toxicol 14, P67 (2013). https://doi.org/10.1186/2050-6511-14-S1-P67

Download citation

Keywords

  • Nitric Oxide
  • Guanylyl Cyclase
  • Regulate Blood Pressure
  • Organ Bath
  • Definitive Role

BMC Pharmacology and Toxicology

ISSN: 2050-6511

Contact us