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Taipan Natriuretic Peptides Are Potent and Selective Agonists for the Natriuretic Peptide Receptor A

Simone Vink1, Kalyana Bharati Akondi2, Jean Jin1

  • 1Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia.

Molecules (Basel, Switzerland)
|April 13, 2023
PubMed

Insights

Snake venom contains natriuretic peptides that may treat hypertension. Taipan natriuretic peptides (TNPs) show potent blood pressure-lowering effects and enhance cardiac reflexes without increasing heart rate.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Cardiovascular Research

Background:

  • Cardiovascular diseases, particularly hypertension, are a leading cause of global mortality.
  • Natriuretic peptides found in snake venoms offer therapeutic potential for cardiovascular conditions.
  • Existing natriuretic peptides like human atrial natriuretic peptide (hANP) have limitations in clinical application.

Purpose of the Study:

  • To identify and characterize novel natriuretic peptides from taipan snake venom (Oxyuranus microlepidotus).
  • To evaluate the potency and selectivity of these peptides for natriuretic peptide receptor A (NPR-A).
  • To assess the in vivo cardiovascular effects of the most promising peptide.

Main Methods:

  • Screening of taipan venom for natriuretic peptides (TNP a-e).
  • Assays measuring cyclic guanosine monophosphate (cGMP) production via rat (rNPR-A) and human (hNPR-A) receptors.
  • In vivo studies in conscious normotensive rabbits to measure blood pressure (BP) and heart rate (HR) responses.
  • Structural analysis of TNPc using 3D modeling.

Main Results:

  • Several TNPs (TNP a-e) were identified, stimulating cGMP production via NPR-A.
  • TNPc and TNPd exhibited significant selectivity for rNPR-A over hNPR-A (100- and 560-fold, respectively).
  • In vivo, TNPc effectively lowered systolic and diastolic BP and enhanced cardiac vagal reflexes without causing tachycardia, unlike hANP.
  • TNPc demonstrated high biological stability and a well-defined 3D structure.

Conclusions:

  • Taipan natriuretic peptides, particularly TNPc, represent potent and selective modulators of the natriuretic peptide system.
  • TNPc's ability to lower blood pressure and facilitate vagal reflexes, coupled with its stability and selectivity, makes it a valuable biological tool.
  • These findings suggest potential therapeutic applications for TNPc in managing hypertension and related cardiovascular diseases.

Keywords:
NMR structureTNP pharmacologypeptide stabilitypeptide synthesistaipan natriuretic peptide

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