Metabolism and Release
The term autacoid originates from the Greek words autos (self) and acos (medicament). Alongside histamine, this group includes prostaglandins, cytokines, and nitric oxide (NO). All of them are characterized by a short duration of action and a local effect.
Histamine synthesis occurs via the decarboxylation of the amino acid histidine. Once formed, the mediator is stored in specialized structures:
- granules of mast cells and basophils;
- enterochromaffin-like cells;
- neurons and epidermal cells.
The release (liberation) of the mediator can occur upon exogenous exposure to venoms from certain snakes and insects. However, in pharmacology, histamine liberators are of particular importance — chemical and medicinal substances that provoke histamine release without involving the immune system. These include the muscle relaxant tubocurarine, morphine, polymyxin, and compound 48/80.
Classification of Histamine Receptors
The mediator's action on target cells is mediated through specific G-protein coupled receptors. There are four main types:
- H1 receptors. Coupled with the Gq protein. Located predominantly on the postsynaptic membrane, in the smooth muscle of the bronchi and intestines. Receptor excitation activates phospholipase C, which cleaves membrane phosphatidylinositol bisphosphate. This leads to the generation of secondary messengers (inositol triphosphate and diacylglycerol), an increase in intracellular calcium ($Ca^{2+}$) levels, and, consequently, smooth muscle contraction.
- H2 receptors. Coupled with the Gs protein. Localized on postsynaptic membranes in the central nervous system and on gastric parietal cells. Activation leads to increased cAMP levels, which stimulates proton (hydrochloric acid) secretion.
- H3 receptors. Coupled with the Gi protein. Unlike the first two types, they are located on the presynaptic membrane and are found predominantly in the central nervous system.
- H4 receptors. Also coupled with the Gi protein. Present in organs of the immune and hematopoietic systems (thymus, spleen, bone marrow, leukocytes), as well as in the liver, lungs, and gastrointestinal tract.
Pharmacological Effects
The systemic action of histamine affects multiple organs, causing diverse reactions:
- Cardiovascular system. In the heart, the mediator causes positive inotropic (increases contractility) and chronotropic (increases heart rate) effects. In blood vessels, it stimulates the endothelial release of nitric oxide (NO), leading to vasodilation and a drop in blood pressure. In the microvasculature, capillary permeability sharply increases. On the skin, this manifests as the "triple response": redness (hyperemia), edema, and a local rise in temperature (subjectively felt as warmth).
- Respiratory system. Marked bronchospasm and stimulation of respiratory tract exocrine gland secretion are observed.
- Gastrointestinal tract. Increased intestinal peristalsis and elevated gastric acid secretion occur.
- Smooth muscle. Spasm occurs in most organs.
- Nervous system. Irritation of sensory nerve endings leads to sensory effects: pruritus (itching, as in urticaria) or pain (as in a bee sting).