Neurokinin A: natural nerve-signalling peptide
A naturally made messenger released by nerves that helps control muscle contraction, inflammation, and pain; not a drug, used mainly as a lab research tool.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
Endogenous peptide — produced naturally and routinely synthesized for research
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Endogenous peptide — receptor binding and activity established in published literature
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What this is
Neurokinin A (NKA) is a short, naturally occurring signalling peptide made in the human body — one of three "tachykinin" messengers that nerves use to talk to muscle, immune, and other tissues. It is co-produced with Substance P from the same gene (TAC1), released together with Substance P from the same nerve terminals, but acts on a different preferred receptor (NK2 rather than NK1). In its mature, active form NKA carries a C-terminal amide (HKTDSFVGLM-NH₂) that is required for binding to the tachykinin receptors and is not represented in the bare 10-letter sequence stored here (Steinhoff 2014). NKA and its relatives are widely studied because the tachykinin system is present throughout the nervous, immune, gastrointestinal, respiratory, and urogenital systems and contributes to pain signalling, inflammation, smooth-muscle contraction, and neurogenic disease (Steinhoff 2014).
History
Tachykinins are one of the most intensively studied neuropeptide families. The modern picture identifies Substance P, NKA, and Neurokinin B as the three primary mammalian members, traces NKA and Substance P to the preprotachykinin A gene (TAC1) and Neurokinin B to a separate gene (TAC3), and assigns each peptide a preferred receptor among the three neurokinin GPCRs NK1, NK2, and NK3 (Steinhoff 2014). Comparative work has shown that the family's C-terminal pharmacophore (Phe-X-Gly-Leu-Met-NH₂) is conserved across vertebrates and invertebrates: a midgut tachykinin from the desert locust Schistocerca gregaria was characterised by mass spectrometry (Veelaert 1999), and an integrated neuropeptidomic study of the tree shrew (Tupaia belangeri) catalogued NKA together with the longer NKA-containing fragments produced from the same precursor (Petruzziello 2012). Beyond its endogenous biology, NKA is of interest because the tachykinin system overlaps with disease pathways — including epilepsy and chronic inflammation — surveyed in reviews of neuropeptides as targets for anticonvulsant drug development (Clynen 2014).
What it does
Inside the body, NKA acts as a fast neuromodulator: it is released from nerve terminals alongside Substance P and triggers responses in nearby cells through tachykinin G-protein-coupled receptors. NKA's preferred receptor is the NK2 receptor (TACR2), which is enriched on smooth muscle and contributes to gut motility, airway tone, and bladder contractility, while Substance P is the preferred ligand at NK1 and Neurokinin B at NK3 (Steinhoff 2014). Because the same tachykinin signalling axis shows up in pain processing, neurogenic inflammation, and seizure circuits, NKA and the broader tachykinin system have been examined as therapeutic targets in respiratory disease, GI disorders, and CNS conditions including epilepsy (Steinhoff 2014; Clynen 2014).
Mechanism
NKA is one of several peptides cleaved from the preprotachykinin A precursor encoded by the TAC1 gene; alternative splicing and post-translational processing of that precursor also yield Substance P and the N-terminally extended forms neuropeptide K (NPK) and neuropeptide γ (NPγ), each of which contains the NKA decapeptide at its C-terminus (Steinhoff 2014; Petruzziello 2012). The mature peptide is C-terminally amidated; this amide, together with the conserved Phe-X-Gly-Leu-Met motif, is the structural feature recognised by the tachykinin receptors. NKA binds all three neurokinin receptors (NK1, NK2, NK3) but with a clear preference for NK2/TACR2 over NK1, which is the structural basis for its distinct physiological profile compared with Substance P (Steinhoff 2014). The conservation of the C-terminal pharmacophore across vertebrate and invertebrate tachykinins — visible in locust Schistocerca gregaria tachykinin (Veelaert 1999) and in non-mammalian vertebrate forms — underlines that the FXGLM-NH₂ end is the receptor-engaging element.
Evidence
- Human: No human clinical trials of Neurokinin A itself are represented in this dossier. Its role in human physiology and disease is established through endogenous-peptide biology and tissue-distribution studies summarised in the tachykinin literature (Steinhoff 2014).
- Animal: Tachykinins including NKA have been studied across mammalian and non-mammalian models, with neuropeptidomic surveys cataloguing NKA and its extended forms in tree shrew brain (Petruzziello 2012) and demonstrating the conservation of the tachykinin family into invertebrates (Veelaert 1999).
- In vitro / reviews: The comprehensive Physiological Reviews synthesis of tachykinins and their receptors covers signalling, trafficking, and disease relevance across the nervous, immune, GI, respiratory, and urogenital systems (Steinhoff 2014); the role of NKA and other neuropeptides as anticonvulsant-drug targets is reviewed in the epilepsy context (Clynen 2014).
Known effects
- Smooth-muscle contraction (gut, airway, bladder) — Mechanistically established via NK2/TACR2 across multiple organ systems (Steinhoff 2014).
- Neurogenic inflammation and pain signalling — Part of the broader tachykinin axis with Substance P (Steinhoff 2014).
- Modulation of seizure-circuit excitability — Proposed target area for anticonvulsant drug development; preclinical and mechanistic (Clynen 2014).
Regulatory status
Neurokinin A is an endogenous human peptide, not a marketed drug. There is no FDA or EMA approval, and no WADA listing, for NKA itself. (Tachykinin-system drugs that have reached the clinic typically act as receptor antagonists — e.g. NK1 antagonists used as antiemetics — rather than as NKA itself; those are separate compounds and outside the scope of this card.)
Related peptides
- Substance P — the most-studied tachykinin; produced from the same TAC1 precursor as NKA and preferring the NK1 receptor (Steinhoff 2014).
- Neurokinin B — third primary mammalian tachykinin, encoded by TAC3, preferring the NK3 receptor (Steinhoff 2014).
- Neuropeptide K (NPK) and Neuropeptide γ (NPγ) — N-terminally extended forms produced from the same preprotachykinin precursor that contain the NKA decapeptide at their C-terminus (Steinhoff 2014; Petruzziello 2012).
Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.
Do NKA and Substance P work together in a multiplying rather than additive way during inflammation?
If these two peptides amplify each other, blocking only one might be nearly useless, suggesting that asthma or chronic pain drugs need to hit both targets at once to work.
Does the charged front portion of NKA prevent it from activating the wrong receptor?
If the front of NKA is a natural selectivity filter, mimicking it could help design drugs that target airway inflammation without triggering pain signalling, benefiting asthma and COPD patients.
Could a single chemical swap make NKA resist destruction in inflamed tissue?
Inflamed tissues destroy NKA quickly by oxidizing one atom in its tail. A stabilized version could stay active longer where it is needed most, potentially improving treatments for asthma or bowel inflammation.
Does NKA cause normal gut movement at low levels but painful spasms at high levels?
If confirmed, this could explain GI symptoms in Crohn's disease and IBS, and point toward fine-tuned NK2-targeting treatments that restore normal digestion rather than just blocking all gut contractions.
Could NKA released by airway nerves push the immune system into allergy mode?
If NKA steers the immune system toward allergy during early exposures, blocking it at that stage could prevent asthma and hay fever from developing in the first place, not just treat symptoms after they appear.
Does the front half of NKA matter at all for gripping the NK2 receptor?
If only the last few amino acids of NKA do the work, drug designers could build much shorter, cheaper molecules that mimic this peptide to treat asthma or irritable bowel syndrome.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.92710942029953 | boltz-2 |
| ranking score | 0.7645934820175171 | boltz-2 |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 1.317 | global PDE — lower = better |
| disorder | NaN | fraction disordered |
▸3-letter notation
▸recipeboltz-2 1.0
| parameter | value |
|---|---|
| model | boltz-2 1.0 |
| weights | — |
| hardware | nvidia_nim_api |
| mlx version | — |
| python | — |
| random seed | — |
| msa strategy | none |
| diffusion samples | 1 |
| runtime | — |
| predicted by | mlx@peptide |
| predicted at | 2026-04-24 |
▸citationbibtex
@peptide{pep04472,
sequence = {HKTDSFVGLM},
target = {tacr2},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}