Histamine

Histamine is a nitrogenous compound involved in digestive mechanisms , in the inflammatory response and as a neurotransmitter in various brain functions. In the human body , histamine is formed by decarboxylation of the amino acid L-histidine, through a reaction catalyzed by the enzyme histidine decarboxylase; its degradation is instead entrusted to histaminase.

Although present in all tissues, histamine is produced, and for the most part stored instantly, especially in mast cells and basophilic granulocytes (cells primarily involved in the allergic and immune response).

Histamine in brief Histamine is a nitrogenous substance involved in many cellular responses, such as inflammatory reactions and gastric secretion . Its massive release by cells involved in the inflammatory and immune response, determines:
→ erythema, wheal (swelling), redness
→ increased production of mucus in the airways (nose and bronchi )
→ appearance of asthma symptoms
→ contraction of the muscles of the intestine ( diarrhea and intestinal cramps ).

Not surprisingly, the excessive release of histamine by these cells plays a leading pathophysiological role in mast cell-dependent inflammatory reactions and IgE-mediated allergic diseases, such as asthma , urticaria , rhinitis and allergic conjunctivitis . It is not even a coincidence that drugs particularly used to prevent these allergic manifestations are called antihistamines, as they are able to counteract the action of histamine at the receptor level.

In addition to the granules of basophils and mast cells, histamine is also found in rather important concentrations in the central nervous system and on the mucosa of the gastrointestinal tract.

Histamine receptors

Histamine performs its action by binding to specific receptors located on the cell membrane, with different effects depending on the site and the type of receptor with which it interacts. Currently, four types of histamine receptors are known, respectively defined as H1, H2, H3 and H4.

 

  Location Main functions
H1 • Endothelial cells ( blood vessels )
• Smooth muscles (bronchi, intestines)
• Adrenal cortex
• Heart
• CNS
EXOCRINE SECRETION: increased production of mucus in the nose and bronchi, resulting in respiratory symptoms.
SMOOTH MUSCULATION OF THE BRONCHI: contraction of the bronchioles with the appearance of typical symptoms of asthma, decrease of lung capacity
SMOOTH MUSCULATION OF THE INTESTINES: contraction that leads to intestinal cramps and diarrhea
INCREASE VASCULAR PERMEABILITY AND VASODILATION
MAINTENANCE OF THE STATE OF ALWAYS;
SENSORY FIBER STIMULATION: pain and itching
H2 • Gastric parietal cells
• Vessel smooth muscles
• Neutrophils • Heart • Uterus
STIMULATION OF GASTRIC SECRETION
VASODILATION: smooth muscle
relaxation INHIBITION OF LEUCOCYTARY FUNCTION UTERINE
CONTRACTION
H3 • CNS, Peripheral nerves (heart, lungs, gastrointestinal tract)
• Enterochromaffin cells
INHIBITION OF NEUROTRANSMITTER RELEASE :
centrally: histamine, acetylcholine , serotonin , dopamine ;
peripherally: norepinephrine and acetylcholine, tachykinins.
GASTRIC SECRETION INHIBITION
H4 • Bone marrow , Spleen
• Eosinophils ; Neutrophils
• Mononuclear, mast cells
IMMUNOMODULATION: modulates the immune and inflammatory responses in the direction of activation

Biological actions of histamine

Histamine is a substance with a vasodilatory, hypotensive and permeabilizing action, all very important characteristics in inflammatory phenomena; the slowing of the blood flow and the increased permeability of the vessels in an area just hit by a trauma, in fact, allows the passage of white blood cells and other substances involved in the confinement and repair of the damage. These actions give rise to the so-called “Triple Response of”, which arises when histamine is injected transdermally:

  • redness (by direct vasodilation);
  • diffuse erythema (due to axon activation);
  • wheal(due to increased permeability).

Look at random, just to remember how everything – when it comes to physiology – makes sense, mast cells are particularly abundant in the sites most exposed to potential tissue lesions (nose, mouth, feet, internal body surfaces, blood vessels, etc.) .

The plasma membrane of mast cells and basophils possess receptors for immunoglobulin class E ( IgE ), typically involved in allergic reactions . Once these antibodies have been activated by a substance recognized as foreign, they bind to basophil and mast cell receptors, behaving in turn as real receptors. From this moment, at each subsequent contact with the antigen, the IgE will stimulate the degranulation of the basophils and mast cells to which they are bound, with consequent release of histamine and other substances involved in the allergic reaction.

At the level of the respiratory system , histamine once again causes dilation of the post-capillary venules and an increase in vascular permeability; it is also associated with a contraction of the bronchial smooth muscles and stimulates mucous secretion. In the presence of excessive bronchoconstriction, the calibres of the airways are reduced to the point of preventing normal oxygenation of the blood, with a sense of suffocation and air hunger . During anaphylaxis , the huge release of histamine and its bronchoconstrictor and local vasodilator effect lead to the occlusion of the respiratory tract with serious danger for the patient’s life.

At the gastric level, the enterochromaffin cells of the bottom of the stomach have the ability to release histamine, which acts in synergy with gastrin by stimulating the secretion of hydrochloric acid and intrinsic factor by the parietal cells, and of pepsin by the peptic cells.

At the enteric level, histamine causes contraction of intestinal smooth muscle, triggering diarrhea at particularly high doses. This occurrence is typical of the consumption of foods rich in histamine (such as poorly fresh fish ) which cause redness of the face and neck, hives, nausea , vomiting , diarrhea, headache , dizziness.

At the dermal level, histamine acts as a powerful stimulant of sensitive nerve endings, especially those that mediate pain and itching; this function is particularly evident following reactions from insect or nettle stings .

In the brain, the neurotransmitter histamine participates in various functions, such as neuroendocrine control, cardiovascular regulation, thermoregulation and wakefulness.

 

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