Atrial and B-type natriuretic peptides are both hormones and clinical biomarkers, and the distinction between those two roles is frequently blurred.
Key Takeaways
- Atrial natriuretic peptide and B-type natriuretic peptide are released from cardiac myocytes in response to wall stretch, promoting natriuresis and vasodilation.
- Both hormones are processed from larger precursors and cleared by receptor-mediated uptake and by neprilysin.
- Distinguish studies of the peptides as biomarkers from studies of them as therapeutic agents.
The family
Atrial natriuretic peptide and B-type natriuretic peptide are released from cardiac myocytes in response to wall stretch, promoting natriuresis and vasodilation. Both act through membrane guanylyl cyclase receptors rather than through G-protein-coupled receptors, which is unusual among peptide hormones.
Biomarker use
B-type peptide and its N-terminal fragment are widely measured in heart failure assessment. Their diagnostic value is well established for specific clinical questions, and it is a separate matter from any therapeutic use of the peptides.
For related mechanism work, see calcitonin peptide.
Cleavage and assay complexity
Both hormones are processed from larger precursors and cleared by receptor-mediated uptake and by neprilysin. Neprilysin inhibition raises circulating levels, which matters both therapeutically and when interpreting biomarker results.
The disulfide ring
A conserved intramolecular disulfide ring is essential for receptor activation, as with several other peptide hormones. Reduction abolishes activity, so the redox state of the sample is analytically relevant.
Interpreting the literature
Distinguish studies of the peptides as biomarkers from studies of them as therapeutic agents. The two literatures are large, distinct, and frequently conflated in secondary sources.
Experimental Conditions and Practical Setup
Assays measure the intact hormone or its stable N-terminal fragment depending on the clinical question, and the analytical target is stated because the two have different clearance and different stability. Neprilysin activity is accounted for in interpretation, since inhibiting it raises measured concentrations independently of any change in secretion.
Biomarker versus therapeutic literature
| Aspect | Biomarker use | Therapeutic use |
|---|---|---|
| Question asked | Does the level aid diagnosis or prognosis? | Does administration improve outcome? |
| Assay target | Intact peptide or N-terminal fragment | Not applicable |
| Confounder | Neprilysin activity, renal function | Receptor desensitisation |
| Evidence base | Large and clinically established | Separate and distinct |
Practical Notes for the Bench
- Separate biomarker literature from therapeutic literature explicitly.
- Account for neprilysin activity when interpreting circulating levels.
- Preserve the conserved disulfide ring; reduction abolishes activity.
Frequently Asked Questions
Are these hormones or biomarkers?
Both. They are hormones with established diagnostic use as biomarkers, and the two literatures should be kept separate.
Why does neprilysin matter?
It degrades the peptides, so inhibiting it raises circulating levels and changes both therapeutic exposure and biomarker interpretation.
What receptor class do they use?
Membrane guanylyl cyclase receptors, which is unusual among peptide hormones.
Does neprilysin inhibition change interpretation of levels?
Yes. Neprilysin degrades these peptides, so inhibiting it raises circulating concentrations and changes both therapeutic exposure and biomarker reading.
Related Reading
- calcitonin peptide
- oxytocin vasopressin peptides
- ghrelin peptide hormone
- residual TFA in peptides
- evaluating peptide research
References & Further Reading
- Kuwahara K et al. The natriuretic peptide system in heart failure: Diagnostic and therapeutic implications. Pharmacol Ther. 2021. PubMed 33894277
- Wu Q et al. Natriuretic Peptide Signaling in Uterine Biology and Preeclampsia. Int J Mol Sci. 2023. PubMed 37569683
- Nersting J et al. Next-Level Natriuretic Peptide Measurement. Clin Chem. 2023. PubMed 36807507
- Peptide literature search on PubMed
- Full-text archive at PubMed Central
- USP general chapters on pharmaceutical analysis
Educational content for research staff. Nothing here should be read as advice on human or veterinary use of any compound.
Reviewed by Priya Raghunathan, MSc, Formulation & Stability Science.