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HISTAMINE

Histamine is formed by decarboxylation of histidine. It is stored preformed in cytoplasmatic granules of mast cells and basophils. Mast cells in man are found in the loose connective tissue of all organs. They occur particularly around blood and lymph vessels around nerves, and are more abundant in the skin, upper and lower respiratory tract, gastrointestinal tract and reproductive mucosa. Mast cells comprise up to 2% of the alveolar tissue cells. They are found especially in the connective tissue beneath the airway basement membrane, the bronchial lumen, near submucosal blood vessels and glands throughout muscle bundles, and in the alveolar septa.

Histamine release

Histamine release can be induced by very many substances:

• IgE
• Complement: C3a, C4a, C5a
• Substance P, somatostatin, neurotensin
• Morphine, endorphins
• Physical stimuli: vibration, heat, cold, sunlight
• ATP
• Histamine-releasing activities (HRA) from lymphocytes, neutrophils, platelets, endothelial cells, human lung macrophages and eosinophils

Histamine receptors

Two histamine receptors have been identified: H1 and H2. Their actions are as follows:

H1

smooth muscle contraction increased vascular permeability increase in cyclic GMP prostaglandin generatione activation of airway vagal afferent nerves pruritus decrease atrioventricular conduction time

H2

gastric acid secretion increased airway mucus secretion increase in cyclic AMP possibly bronchodilation in human subjects esophageal contraction sstimulation of suppressor T-cells inhibition of basophil histamine release inhibition of neutrophil chemotaxis and enzyme release

Effects of histamine on airways

Briefly histamine causes airway narrowing as follows:

• Bronchoconstriction by stimulation of H1 receptors on smooth muscles.
• Mucosal edema from increased microvascular permeability (H1) leading to transudation of fluid and macromolecules through wide intercellular gaps (> 12 nm). In addition, perfusion of previously non-perfused capillary beds may contribute to mucosal edema.
• Stimulation of lung irritant receptors can induce airway smooth muscle contraction through vagal (cholinergic) pathways.
• Direct stimulation of vagal (cholinergic) nerves can induce airway smooth muscle contraction.
• Vagal postganglionic receptors can induce airway smooth muscle contraction.
• Stimulation of H1 receptors increases mucus secretions, and stimulation of H2 receptors increases mucus viscosity.

Histamine is metabolized within minutes and therefore by itself does not accumulate. However, an effect of inhaled histamine on airway diameter in usual dosages may be detectable for up to 70 minutes. Therefore, when subsequent doses are inhaled a small cumulative effect is to be expected.

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