Neurokinin A
Also known as: Substance K, Neuromedin L, NKA, tachykinin-2, neurokinin-A, beta-substance P
Endogenous tachykinin neuropeptide; NK2R-preferring agonist
What it is
People with asthma, irritable bowel syndrome, or neuroendocrine tumours may encounter Neurokinin A — an endogenous signalling peptide measured as a diagnostic biomarker and used in controlled airway challenge research. It is not an approved drug; its primary clinical value today is as a blood test that tracks tumour activity and as a pharmacological tool in asthma studies.
The scientific side
neurokinin A (NKA) is an 10-amino acid tachykinin neuropeptide encoded by the preprotachykinin A (TAC1) gene, which also encodes substance P. NKA binds preferentially to the neurokinin 2 receptor (NK2R), a G protein-coupled receptor (GPCR), with secondary activity at NK1R. Upon NK2R activation, NKA initiates Gq-mediated phospholipase C signalling, elevating intracellular calcium and activating protein kinase C, which drives contraction of smooth muscle in airways, gut, and vasculature. In the respiratory system, NKA is stored in sensory nerve terminals of non-adrenergic non-cholinergic (NANC) neurons within the bronchial mucosa and submucosa. Released by noxious stimuli including allergens, cigarette smoke, ozone, and viral infections, it causes concentration-dependent bronchoconstriction, plasma protein extravasation, and mucus hypersecretion. Clinical bronchoconstriction challenge studies demonstrate that inhaled NKA produces a dose-related fall in FEV1 in asthmatic subjects, with PC20 values closely correlated with methacholine sensitivity, confirming direct smooth muscle contractility via NK2R and indirect neurogenic amplification via NK1R-mediated mast cell degranulation. Inhaled corticosteroids, leukotriene receptor antagonists, and loop diuretics all attenuate NKA-induced bronchoconstriction through distinct mechanisms, validating NKA challenge as a multi-pathway airway pharmacology model. In the gastrointestinal tract, NKA stimulates colonic and small intestinal smooth muscle contraction via NK2R, facilitating propulsive motility; NK2R antagonists such as nepadutant block NKA-induced acceleration of the migrating motor complex in human volunteers. In the central and peripheral nervous system, NKA co-localises with substance P in dorsal root ganglion neurons and spinal cord, where it amplifies nociceptive signalling via NK1R/NK2R on post-synaptic dorsal horn neurons. In neuroendocrine tumour biology, NKA is secreted by enterochromaffin and midgut neuroendocrine tumour cells into the circulation, where plasma NKA concentration serves as a prognostic biomarker; levels above 50 ng/L associate with significantly shorter overall survival in metastatic small bowel neuroendocrine tumours. Emerging research demonstrates NK2R as a promising pharmacological target for obesity and metabolic disease, as receptor activation simultaneously reduces food intake and increases thermogenic energy expenditure in preclinical models, prompting structural and synthetic efforts to develop selective NK2R agonists free of NKA's off-target NK1R-mediated cardiovascular side effects.
Class: Endogenous tachykinin neuropeptide; NK2R-preferring agonist
Administration & storage
- Administration
- Inhaled nebulisation for airway challenge studies in asthmatic subjects (clinical research only — not therapeutic)Intravenous infusion for gastrointestinal motility research in human volunteers (pharmacological challenge only)Intrathecal injection in animal models for nociception researchIntraperitoneal and subcutaneous injection in rodent models for metabolic and voiding studies
- Storage
- Lyophilised synthetic NKA: store desiccated at -20°C or below; protect from moisture and light. Reconstituted solutions: store at -80°C in single-use aliquots to avoid freeze-thaw degradation; NKA is susceptible to enzymatic cleavage by neutral endopeptidase (neprilysin), angiotensin converting enzyme, and aminopeptidase N. Clinical plasma samples for NKA biomarker measurement: collect into EDTA tubes with added peptidase inhibitors (aprotinin); centrifuge immediately and store plasma at -80°C until assay. Room-temperature stability is limited to a few hours.
- Cautions
- Transient hypotension: IV and inhaled NKA can cause dose-related blood pressure reduction via NK1R-mediated vasodilation. This is especially relevant at higher doses. Blood pressure monitoring is required in all clinical research protocols using IV NKA infusion.,Bronchoconstriction risk: Inhaled NKA challenge in asthmatic subjects carries risk of severe bronchospasm. Challenges must only be performed in settings with immediate access to inhaled bronchodilators, resuscitation equipment, and trained medical personnel. Subjects with FEV1 <70% predicted should not undergo NKA challenge.,Off-target NK1R activity: Native NKA has measurable binding affinity at NK1R in addition to NK2R, which mediates nausea, vomiting, neurogenic inflammation, and cardiovascular effects including tachycardia and hypotension at higher concentrations. This cross-reactivity is the primary pharmacological limitation of NKA versus selective NK2R agonists.,No therapeutic self-administration evidence: Neurokinin A has no established therapeutic indication and no approved drug formulation. There are no documented protocols for self-administration of exogenous NKA in any clinical context. Any self-administration outside a regulated clinical trial constitutes off-label experimental exposure of unknown risk.,Enzymatic degradation: NKA is rapidly degraded in plasma and tissues by neprilysin and ACE, resulting in a very short plasma half-life (minutes). This limits its practical utility as an exogenously administered therapeutic and means that dosing and timing are critical in any research application.
Legal & regulatory status
Neurokinin A is not approved by the US FDA as a therapeutic drug. It is an endogenous neuropeptide used as a research tool and pharmacological challenge agent (e.g., inhaled NKA bronchoconstriction challenge in asthma…
Neurokinin A is an endogenous peptide and is not specifically listed on the WADA Prohibited List. However, it is a tachykinin neuropeptide and any synthetic analogues developed to stimulate NK2 receptor-mediated effects…
Neurokinin A has no approved therapeutic indication in Canada. It is not listed as a regulated drug product. NKA is used as a research pharmacological challenge agent in academic clinical studies. Its measurement in…
What it's studied for
- Asthma — pharmacological bronchial challenge model to assess airway neurogenic inflammation and treatment efficacy Human RCT
- Asthma severity biomarker — sputum and airway NKA as a measure of neurogenic airway inflammation Human observational
- Gastrointestinal motility — NKA-stimulated small intestinal and colonic contraction; NK2R antagonist pharmacology Human RCT
- Neuroendocrine tumour (NET) biomarker — plasma NKA as a prognostic marker in midgut small bowel NETs Human observational
- Pain processing and nociception — NKA as a spinal cord neurotransmitter amplifying pain signalling Preclinical (Animal)
- Neonatal pain assessment — plasma NKA as a biochemical measure of pain response in neonates Human observational
- Obesity and metabolic disease — NK2R activation as a dual food intake suppression / energy expenditure mechanism Preclinical (Animal)
- Underactive bladder and bowel — NK2R agonism as a pro-voiding strategy Preclinical (Animal)
Safety signals
- Bronchoconstriction and bronchospasm in asthmatic subjects
- Transient hypotension and cardiovascular effects via NK1R cross-reactivity
- Nausea and emetic response
- Neurogenic inflammation — plasma protein extravasation and oedema
- Intestinal hypermotility and diarrhoea
- Rapid enzymatic degradation limiting predictable pharmacokinetics
- Potential role in airway remodelling and chronic neurogenic inflammation with sustained elevation
All studies (3)
Frequently asked
What is Neurokinin A and why would someone be tested for it?
Neurokinin A (NKA) is a short signalling peptide produced naturally by your nervous system and by certain tumour cells. Most people encounter it as a diagnostic blood test rather than as a drug. Clinicians measure plasma NKA levels in patients suspected of having — or being monitored for — neuroendocrine tumours of the small bowel, where an elevated NKA above approximately 50 ng/L signals a worse prognosis and guides treatment decisions. NKA is not a drug you take; it is something your body produces, and its level is measured to track tumour activity.
Is Neurokinin A used as a peptide for bodybuilding or performance enhancement?
No. There is no evidence in the published literature that Neurokinin A is used in bodybuilding, athletic performance enhancement, or peptide self-administration communities. NKA is an endogenous neuropeptide with a plasma half-life of minutes; it is not orally active and degrades rapidly after injection. Its primary receptor (NK2R) has some preclinical interest in metabolic research, but NKA itself has not been developed as a therapeutic or self-administration product. Any self-injection of NKA outside a supervised clinical trial would carry unknown and potentially serious cardiovascular and respiratory risks.
How does Neurokinin A relate to asthma?
In asthma, your airway sensory nerves release Neurokinin A (along with substance P) when irritated by allergens, cold air, smoke, or exercise. NKA binds to receptors on airway smooth muscle and causes bronchoconstriction — airway narrowing — as well as mucus production and airway swelling. Researchers have used inhaled NKA as a controlled bronchial challenge to study how well anti-asthma drugs work. Multiple clinical trials have shown that inhaled corticosteroids (like fluticasone) and leukotriene blockers (like montelukast) reduce the airway's sensitivity to NKA, explaining part of how these drugs relieve asthma symptoms.
Can Neurokinin A levels in the blood tell me if I have a neuroendocrine tumour?
Elevated plasma Neurokinin A can be a useful clue, but it is not a standalone diagnostic test. NKA is measured alongside chromogranin A, urinary 5-HIAA, and serotonin as part of a panel of neuroendocrine tumour (NET) biomarkers, primarily for midgut (small bowel) NETs. An NKA above 50 ng/L is strongly associated with worse outcomes, but NKA can be elevated in other conditions. Clinical studies have shown that a single NKA measurement has limited sensitivity on its own; a multimarker approach or molecular blood test (such as the NETest PCR panel) performs better for initial diagnosis. Your doctor uses NKA results in the context of symptoms, imaging, and other laboratory tests.
What is the difference between Neurokinin A, Substance P, and Neurokinin B?
Neurokinin A (NKA) and Substance P (SP) are both encoded by the same gene (TAC1) and are released together from sensory nerve terminals. SP has the highest affinity for NK1 receptors, while NKA preferentially activates NK2 receptors. Both contribute to neurogenic inflammation, bronchoconstriction, gut motility, and pain. Neurokinin B (NKB) is encoded by a different gene (TAC3), preferentially activates NK3 receptors, and plays a major role in regulating reproductive hormone pulses via KNDy neurons in the hypothalamus — a quite different physiological role from NKA. In practical terms: SP and NKA act together in the airways and gut; NKB is more relevant to reproductive neuroendocrinology.
Are there any drugs that block Neurokinin A?
Several drugs that block Neurokinin A's main receptor (NK2R) have been investigated clinically, though none is widely approved specifically for this purpose. Ibodutant is an NK2R antagonist that reached Phase III clinical trials for irritable bowel syndrome with diarrhoea (IBS-D) in women. Several dual NK1/NK2 antagonists — including AVE5883 and FK224 — were tested in asthma clinical trials and showed biological activity against NKA-induced bronchoconstriction. However, none of these compounds achieved regulatory approval for asthma. Aprepitant and related neurokinin antagonists primarily block NK1R (substance P's receptor) and are approved for nausea prevention; they have only indirect effects on NKA-mediated pathways.