Histamine is not a hormone; it is a biogenic amine. This molecule functions primarily as an autacoid, or “local hormone,” and also as a neurotransmitter involved in local communication between cells. Confusion about its classification arises because histamine regulates widespread processes, including immediate immune defense, gastric acid production, and the sleep-wake cycle. Unlike true hormones, which are produced by specific endocrine glands and travel through the bloodstream to distant organs, histamine largely acts immediately and locally near its site of release.
What Histamine Actually Is
Histamine is classified as a multifaceted signaling molecule, primarily functioning as an autacoid and a neurotransmitter. Autacoids are biological substances synthesized in various tissues that act locally, exerting their effects at or near the site of their synthesis before being rapidly broken down. This contrasts sharply with hormones, which are secreted by endocrine glands, circulate in the blood, and act on distant target cells.
Histamine’s effects are typically short-lived and restricted to the surrounding area, a process known as paracrine or autocrine signaling. Furthermore, histamine acts as a neurotransmitter in the brain, sending signals between nerve cells, a function distinct from endocrine signaling.
The Immediate Immune Response
Histamine is most widely known for its central function in the body’s immediate defense system against foreign invaders and injury. The molecule is synthesized and stored in high concentrations within tiny storage sacs, called granules, primarily inside mast cells and basophils. Mast cells are strategically positioned in tissues exposed to the outside world, such as the skin, lungs, and gastrointestinal tract, acting as sentinels.
When the body encounters a threat, such as an allergen, the immune system triggers a rapid release of histamine from these storage granules, a process called degranulation. The sudden influx of histamine initiates the familiar symptoms of an allergic reaction or inflammation. Histamine binds to H1 receptors, causing blood vessels to widen—a process called vasodilation—which increases blood flow to the affected area, leading to redness and warmth.
In addition to vasodilation, histamine increases the permeability of small blood vessels. This allows fluid, proteins, and immune cells to leak out of the bloodstream and into the surrounding tissue, resulting in swelling and puffiness. The stimulation of sensory nerve endings by histamine also causes the sensation of itching.
Systemic Roles in Digestion and Sleep
Histamine performs specific, non-immune regulatory functions in other body systems. In the gastrointestinal tract, histamine plays an important part in the process of digestion. It is released by specialized cells in the stomach lining, called enterochromaffin-like (ECL) cells, and acts on H2 receptors found on parietal cells.
Activation of these H2 receptors potently stimulates the secretion of hydrochloric acid into the stomach lumen. This acid is necessary for breaking down food and activating digestive enzymes. Histamine is considered a final common mediator of acid secretion, working in coordination with other chemical signals like gastrin and acetylcholine.
In the brain, histamine acts as a powerful neurotransmitter, regulating the sleep-wake cycle and promoting wakefulness. Histaminergic neurons originating in the hypothalamus fire rapidly during wakefulness and slow down during non-rapid eye movement (NREM) sleep, becoming nearly silent during rapid eye movement (REM) sleep. Histamine binds to H1 receptors in the brain to promote alertness and arousal. This neurological activity explains why some older allergy medications that block histamine’s action in the brain often cause drowsiness as a side effect.
Targeting Histamine: How Medications Work
The widespread effects of histamine are mediated through four different types of cellular receptors, labeled H1, H2, H3, and H4, each triggering a different response. Medications designed to counteract histamine’s effects are called antihistamines, which work by blocking histamine from binding to these specific receptors. They do not stop the body from producing histamine but prevent it from causing downstream effects.
The most common medications, used to treat allergies, are H1-antihistamines, which block the H1 receptors responsible for allergic symptoms like itching, sneezing, and swelling. Due to the presence of H1 receptors in the brain, first-generation H1 blockers can cross the blood-brain barrier and cause sedation.
A different class of medication, the H2-antihistamines, specifically targets the H2 receptors in the stomach. By blocking these receptors, H2 blockers reduce the production of stomach acid, making them effective treatments for conditions like heartburn and peptic ulcers.