Serpinin
An endogenous chromogranin-A peptide that strengthens the heartbeat — the opposite of its cousins catestatin and vasostatin. A research peptide, not a drug
Serpinin is a small peptide cut from the tail end of chromogranin A, the same large precursor protein that gives rise to the heart-calming peptides catestatin and vasostatin. It comes in a few closely related forms — plain serpinin, a chemically capped version called pyroglutaminated serpinin (pGlu-serpinin), and an extended form — and it is interesting because it does the opposite of its chromogranin-A cousins. Where catestatin and vasostatin dampen the heart by acting like beta-blockers, serpinin and especially pGlu-serpinin act like beta-adrenergic agonists: they make the heart contract harder and relax faster, working through the beta1-adrenergic receptor and the cAMP/PKA pathway. pGlu-serpinin also protects heart muscle from the damage of ischemia and reperfusion and shields cells and neurons from stress-induced death, and plain serpinin signals endocrine cells to rebuild their secretory granules. Serpinin is studied as a research tool for understanding how chromogranin A fine-tunes the heart and secretory cells; it is not an approved medicine and has not been given to people as a treatment.
No established human dose Details ↓
Recommended Dosing
No established human dose
Serpinin is an endogenous human peptide that has never been given to people as a treatment. The work is in animals, isolated organs and cells, where serpinin and pGlu-serpinin are applied at experimental nanomolar concentrations that do not carry over to people.
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What is it?
Chromogranin A is a large acidic protein packed into the secretory granules of endocrine, neuroendocrine and heart cells, and it is chopped by processing enzymes into a set of smaller active peptides. The best-known of these — vasostatin-1 and catestatin — act as brakes on the heart, suppressing contractility in a beta-blocker-like way. Serpinin is a more recently described member of the set, cut from the very end (the C-terminus) of chromogranin A. It occurs in three forms: serpinin itself, a chemically modified pyroglutaminated form (pGlu-serpinin), and a longer serpinin-RRG.
What makes serpinin stand out is that it reverses the usual chromogranin-A script on the heart. In the isolated rat heart, serpinin and the more potent pGlu-serpinin produce dose-dependent positive inotropic (stronger contraction) and lusitropic (faster relaxation) effects within minutes, acting through the beta1-adrenergic receptor and the adenylate-cyclase/cAMP/PKA pathway — in other words, like a beta-adrenergic agonist rather than the beta-blocker-like vasostatin and catestatin. pGlu-serpinin is effective from very low (nanomolar) concentrations.
pGlu-serpinin is also protective. Given to isolated rat hearts before or after a period of no blood flow, it reduced the size of the resulting infarct and helped the heart recover, in both normal and hypertensive animals, through the classic pro-survival 'reperfusion injury salvage kinase' pathways; direct experiments on heart-muscle cells confirmed the protection. Beyond the heart, pGlu-serpinin guards pituitary cells and brain neurons against oxidative-stress-induced death, pointing to a neuroprotective role.
Plain serpinin has a distinct job inside the cell. Secreted from pituitary cells on stimulation, it signals back to raise production of a protease inhibitor called protease nexin-1, which protects granule proteins from being degraded and so drives the rebuilding of secretory granules after they are released — a feedback loop that keeps endocrine cells stocked. Serpinin is also found in sensory nerves, including those of the skin, alongside substance P.
Serpinin is an endogenous human peptide and a research tool, not a medicine. No published study has given serpinin to people as a treatment — the work is in animals, isolated organs and cells — it is approved nowhere, and material sold online as 'serpinin' is an unregulated research chemical. Nothing here is a dose or a therapy; this page records what the published science says about the peptide.
Mechanism of Action
Serpinin and pyroglutaminated serpinin are chromogranin-A C-terminal peptides that act as beta-adrenergic-like positive modulators of the heart (through beta1-AR/cAMP/PKA), protect heart muscle and neurons from stress, and drive secretory-granule biogenesis in endocrine cells.
Secretory-granule biogenesis
Plain serpinin raises protease nexin-1 via cAMP/PKA/Sp1, protecting granule proteins and driving the rebuilding of secretory granules in endocrine cells (PMID 21436258).
Published Research
These are studies of serpinin read from their PubMed abstracts on November 6, 2026. They include a review of the serpinin peptides, an isolated-heart study showing serpinin and pGlu-serpinin are positive cardiac inotropes, an animal study of pGlu-serpinin cardioprotection in ischemia/reperfusion, a comparative study in fish and amphibian hearts, a cell study of serpinin driving secretory-granule biogenesis, and a cell/neuron study of pGlu-serpinin inhibiting cell death. Serpinin has not been given to people as a treatment in any published study; the evidence is animal, isolated-organ and cell work.
Serpinins: granule biogenesis, cell death and cardiac function
A review of the serpinin peptide family (serpinin, pGlu-serpinin and serpinin-RRG), cut from the C-terminus of chromogranin A. Serpinin up-regulates protease nexin-1 to drive secretory-granule biogenesis via a cAMP-PKA-Sp1 pathway; pGlu-serpinin protects neurons and pituitary cells against oxidative stress and, in the isolated rat heart, exerts a concentration-dependent positive inotropic effect through a cAMP-PKA pathway — profound effects across endocrine, nervous and cardiac systems.
Serpinin and pGlu-serpinin are positive cardiac inotropes
Serpinin peptides were detected in the rat heart, and in the isolated perfused heart serpinin and pGlu-serpinin exerted dose-dependent positive inotropic (stronger contraction) and lusitropic (faster relaxation) effects within 5 minutes, pGlu-serpinin being the more potent (from 1 nM). Both acted through a beta1-adrenergic receptor / adenylate cyclase / cAMP / PKA pathway — making them beta-adrenergic-like agonists, the opposite of the beta-blocker-like vasostatin-1 and catestatin (an isolated-organ result).
pGlu-serpinin protects the heart from ischemic injury
In isolated hearts from normal and hypertensive rats, pGlu-serpinin given before ischemia (preconditioning) or at reperfusion (postconditioning) reduced infarct size and aided recovery, being especially protective in hypertensive hearts at reperfusion. The protection was blocked by inhibitors of the pro-survival PI3K/Akt, mitochondrial-KATP and PKC pathways, and pre-treating heart-muscle cells protected them against hypoxia/reoxygenation (a preclinical result).
Serpinin in fish and amphibian hearts
Testing serpinin and pGlu-serpinin on isolated working hearts of eel, goldfish and frog, pGlu-serpinin reduced stroke volume in all three species, while plain serpinin reduced contractility only in the frog. In goldfish and frog the effect ran through a nitric-oxide/cGMP pathway. The comparative result supports an evolutionarily conserved role for the chromogranin-A serpinin system in the sympatho-adrenergic control of the vertebrate heart (a preclinical result).
Serpinin drives secretory-granule biogenesis
A 2.9-kDa chromogranin-A C-terminal peptide, named serpinin, was identified in the medium of pituitary cells. Secreted on stimulation, it raised transcription of the protease inhibitor protease nexin-1 through a cAMP / PKA / Sp1 pathway, which protects granule proteins from degradation and promotes the rebuilding of secretory granules — an autocrine feedback loop by which serpinin replenishes released granules in endocrine cells (a cell result).
pGlu-serpinin inhibits cell death
Pyroglutaminated serpinin (pGlu-serpinin), a 23-residue chromogranin-A-derived peptide secreted from pituitary cells, prevented oxidative-stress (hydrogen-peroxide)-induced death of pituitary cells and cultured brain neurons at low nanomolar concentrations, and raised protease nexin-1 levels. The anti-apoptotic effect suggests a neuroprotective role for pGlu-serpinin in the nervous system and pituitary (a cell-culture result).
No Established Human Dose
Serpinin is an endogenous human peptide that has never been given to people as a treatment. The work is in animals, isolated organs and cells, where serpinin and pGlu-serpinin are applied at experimental nanomolar concentrations that do not carry over to people. No regulator has approved any dose, and no published human dose exists, so no amount is printed here.
What this rests on: PMID 22459152, PMID 26400960, PMID 22834799.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Serpinin is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of Serpinin has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Serpinin, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Serpinin stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Serpinin. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
How long it stays in the body: a half-life of not established for humans as a drug; an endogenous signalling peptide. After about five half-lives almost none is left.
When effects appear: unknown; no source on this page gives a time to effect for Serpinin. Results reported in the studies are under Published Research.
Source: half-life: PMID 22834799.
Side effects, and when to stop or get help
From the Side Effects section: No human adverse-event data exist: no published study has administered serpinin to people; Serpinin and pGlu-serpinin are beta-adrenergic-like positive cardiac stimulants in animal hearts (PMID 22459152), so cardiovascular effects would be expected if administered; pGlu-serpinin is cardioprotective in ischemia/reperfusion models (PMID 26400960) — a preclinical finding, not an established human effect; Material sold online as 'serpinin' is an unregulated research chemical of unverified content. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Serpinin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Serpinin is an endogenous peptide that has not been given to people as a drug, so there is no human safety profile; the points below reflect that research status”).
Interactions
Unknown: a PubMed search for human interaction studies of Serpinin (reviewed 2026-11-06) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Serpinin products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a drug: Drugs@FDA and the openFDA label endpoint hold no record, and FDA GSRS and ChEMBL hold no substance record for serpinin (searched November 6, 2026)). Sport: Not on the 2026 List.
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
Serpinin is an endogenous peptide that has not been given to people as a drug, so there is no human safety profile; the points below reflect that research status.
Contraindications & Cautions
Serpinin has no approved use and no label. These points reflect its endogenous, research status.
Legal Status
Serpinin is an endogenous human peptide studied as a research compound; it is not a drug and is not approved in any country.
Frequently Asked Questions
?What is serpinin?
An endogenous human peptide cut from the C-terminal end of chromogranin A — the same precursor that yields catestatin and pancreastatin. It occurs as serpinin, a capped form called pGlu-serpinin, and a longer serpinin-RRG.
?What does it do?
It strengthens the heartbeat and speeds relaxation like a beta-adrenergic agonist (the opposite of its cousins catestatin and vasostatin), through the beta1-receptor/cAMP/PKA pathway (PMID 22459152); pGlu-serpinin protects the heart from ischemic injury (PMID 26400960) and cells from death (PMID 21537909), and serpinin drives secretory-granule rebuilding (PMID 21436258).
?Is it a treatment for anything?
No. Serpinin is a research peptide used to study how chromogranin A modulates the heart and secretory cells. No human trial has administered it, and it is approved nowhere.
?Is it approved or available to buy?
No. Serpinin is not a medicine, has no FDA application or label, and is approved nowhere. Material sold online as serpinin is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source; this page records the published science.
References
- [review] Loh YP, et al. "Serpinins: role in granule biogenesis, inhibition of cell death and cardiac function." Curr Med Chem, 2012;19(24):4086-92. PMID: 22834799.
- [mechanism] Tota B, et al. "The novel chromogranin A-derived serpinin and pyroglutaminated serpinin peptides are positive cardiac β-adrenergic-like inotropes." FASEB J, 2012;26(7):2888-98. PMID: 22459152.
- [animal] Pasqua T, et al. "pGlu-serpinin protects the normotensive and hypertensive heart from ischemic injury." J Endocrinol, 2015;227(3):167-178. PMID: 26400960.
- [animal] Imbrogno S, et al. "The Chromogranin A-derived sympathomimetic serpinin depresses myocardial performance in teleost and amphibian hearts." Gen Comp Endocrinol, 2017;240:1-9. PMID: 27633326.
- [mechanism] Koshimizu H, et al. "Serpinin: a novel chromogranin A-derived, secreted peptide up-regulates protease nexin-1 expression and granule biogenesis in endocrine cells." Mol Endocrinol, 2011;25(5):732-44. PMID: 21436258.
- [mechanism] Koshimizu H, et al. "Role of pGlu-serpinin, a novel chromogranin A-derived peptide in inhibition of cell death." J Mol Neurosci, 2011;45(2):294-303. PMID: 21537909.
- [other] UniProt P10645 (CMGA_HUMAN), read November 6, 2026: the serpinin peptides are produced by proteolytic cleavage at pairs of basic residues in the conserved C-terminus of chromogranin A, the product of the CHGA gene and a member of the granin family. https://www.uniprot.org/uniprotkb/P10645/entry
- [other] Serpinin was identified as a ~2.9-kDa chromogranin A C-terminal peptide; three forms occur — serpinin, pyroglutaminated (pGlu)-serpinin and serpinin-RRG — and their biology is set out in the serpinin reviews carded on this page (read November 6, 2026).
- [other] US FDA, Drugs@FDA and the drug label endpoint (openFDA), searched November 6, 2026: no application and no label record for serpinin. It is an endogenous human peptide, not a registered drug; FDA GSRS and ChEMBL hold no substance record for it.
Sources & Citations
The six studies carded above were read from their PubMed records on November 6, 2026. Identity comes from UniProt (P10645, gene CHGA); serpinin's origin from the chromogranin-A C-terminus, its three forms, its beta-adrenergic-like positive cardiac action (contrasting catestatin and vasostatin), its cardioprotective and anti-apoptotic effects and its role in granule biogenesis are from the reviews and studies carded here; the absence of US approval and of a drug substance record from Drugs@FDA, openFDA, FDA GSRS and ChEMBL was checked the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.