Human Histamine ELISA Kit

Histamine is a biogenic amine and is involved in a lot of the body's biology. It's famous for immune reactions – allergies particularly – but it does so much more. Histamine is made from the amino acid histidine and decarboxylated with the enzyme histidine decarboxylase. After it's created, histamine does its work, attaching itself to a histamine receptor on any cell or tissue in the body. Each of these receptors (H1, H2, H3, H4) disturbs one biological process — the immune system, stomach acid secretion, neurotransmission, smooth muscle contractility. It's a tricky one, this histamine's behaviour spectrum, and it's what drives life and death. Histamine is usually referring to the body's immune response to allergens: it shoots from mast cells and basophils as an immune response. Histamine does this by promoting vasodilation and expanded blood vessels to produce the familiar allergic reactions: swelling, redness and itching. Not only is histamine for allergy, but also has powerful activity in gut modulation, by increasing gastric acid via H2 receptors on parietal gut cells. It's an essential GI maneuver as the stomach acid dissolves and digests food. It's also a central nervous system neurotransmitter, and histamine regulates arousal, wakefulness and hunger. With histamine receptors found everywhere, it's at work on every kind of physiological function, well-known or not. The H3 receptor, for instance, only in the brain modulates other neurotransmitters – dopamine, serotonin, etc. – that regulate mood, cognition and motor function. Instead, it's the H4 receptor, more common on immune cells, that's involved in inflammation and in initiating immune cell migration towards an infection or injury. Such obscure but fundamental functions are proof that histamine has far more consequences than its initial connection with allergy.

Figure 1. Overview of the main functions of the histamine receptors. (Sources:Tiligada E, et al. 2020)

Histamine is an important immune messenger for allergic and inflamatory reactions. When an allergen – for example, pollen or dust mites – is brought into the body, antibodies called immunoglobulin E (IgE) will kick in. Such IgE antibodies attach to mast cell and basophil receptors – prevalent in tissues exposed to the external environment such as skin, lungs and gut. After being exposed to another allergen, the allergen binds to IgE antibodies present on mast cells, which releases histamine and other inflammatory molecules (cytokines, prostaglandins). The histamine releases many of the physiological responses that we associate with an allergic reaction. Histamine snatches at H1 receptors on smooth muscle cells and stimulates their contraction, which narrows the airways in asthma. It also works on the endothelial cells that cover blood vessels, opening them up so immune cells and proteins can flow through it to the place of infection or damage. This process results in the redness, swelling and itching that allergic reactions are known for. At worse – in anaphylaxis, for instance – histamine also releases vasodilation across the entire body, resulting in deadly loss of blood pressure, shock and organ failure. Yet histamine isn't just an immune system player in acute hypersensitivity syndromes. Histamine also functions to recruit immune cells to tissues damaged or infected, as in chronic inflammation and autoimmune conditions. Histamine latches on to H4 receptors on immune cells, and through movement and activity generates inflammatory disorders. Histamine is involved in the re-stimulation of the immune system when diseases like rheumatoid arthritis and inflammatory bowel disease destruct tissues and exacerbate pain. Histamine's immunologic role, then, is complex, ranging from allergy to the perpetuation of chronic inflammation and immune cell activation. Histamine isn't just an immune system neurotransmitter: it's a CNS neurotransmitter. Neuromodulator histamine keeps the brain on its toes, from sleep to learning to appetite. Histamine neurons – of which there are most in the hypothalamus – run through the brain and spinal cord, and their effects are felt in hundreds of neurological pathways. Such histaminergic neurons are at the busiest while we're awake and thought to keep us awake. Rather, they're much less mobile during sleep, and in particular during rapid eye movement (REM) sleep – all of which points to a link between histamine and sleep-wake cycles. Histamine works by interacting with H1 and H3 receptors in the brain. The H1 receptor, which it fires in the brain, can rouse and alert you. And that's why antihistamines – drugs that block H1 receptors – put us to sleep, because they turn histamine's electrical firing off the brain. The H3 receptor, by contrast, is an auto-receptor that turns off histamine production and controls other neurotransmitters like dopamine, serotonin and acetylcholine. That syncing of neurotransmitter releases controls mood, cognition and movement. Histamine's tinkering on these receptors is the secret to mental sharpness, attention and emotion regulation. Other studies, too, want to see how histamine might be used in psychiatric and neurodegenerative disorders. It was demonstrated that histamine signalling has shifted even in schizophrenia, attention-deficit/hyperactivity disorder (ADHD) and Parkinson's. In schizophrenia, for instance, over-activity of histamine's dopaminergic modulators might be the source of the patient's psychotic symptoms. Histamine as motor control is especially interesting in Parkinson's, where disruptions of histamine signalling have been linked to movement-related symptoms. Therefore, histamine-based therapies are being studied as treatment or relief of symptoms in such diseases. This interplay between histamine and the brain means there is still more work to be done to learn how it functions both in normal brain functioning and in disease.

Histamine's role in the gut – through the release of gastric acid – is another aspect of its work in human biology. Enterochromaffin-like cells (ECL cells) make histamine in the stomach lining. When released, histamine binds to H2 receptors on parietal cells in the wall of the stomach, to release gastric acid. It's a digestive acid, because it breaks down food and kicks in enzymes like pepsin that break down proteins. Gastric acid released by the H2 receptor is one of the main processes responsible for adjusting stomach pH and digestion. The release of gastric acid is precisely tuned and histamine releasing is influenced by a variety of factors. When, for example, the stomach contains food, gastrin – which also catalyses histamine production – is released. Further, histamine can also boost other digestive enzymes, such as pepsinogen (broken down into pepsin by acid in the stomach's environment). Histamine's digestion functions are critical, but excessive or unbalanced gastric acid leads to gastrointestinal illnesses such as gastroesophageal reflux disease (GERD), peptic ulcers and Zollinger-Ellison syndrome. In such cases, the excess gastric acid creates lining of stomach and esophagus that will result in heartburn, ulcers and indigestion. The drugs to treat these are H2 receptor antagonists (h2 blockers). These drugs squelch histamine's binding of ligands to the H2 receptor, which lowers gastric acid and eases the effects of acidic illness. For GERD, peptic ulcers and gastritis, there are drugs like ranitidine and famotidine dating back decades. But the discovery of proton pump inhibitors (PPIs) that trigger acid generation have altered treatment protocols. This is not to say that histamine's role in managing gastric acid is still new, and that H2 blockers are still available in some medical settings illustrates just how crucial histamine's role in managing gastric health really is.

2-(1H-imidazol-4-yl)ethanamine
4-Imidazoleethylamine
Histamine H1 receptor agonist
Endogenous biogenic amine
Beta-imidazoleethanamine