Pathophysiological Roles of Histamine

PATHOPHYSIOLOGICAL ROLES - HISTAMINE

Gastric Secretion

Histamine has dominant physiological role in mediating secretion of HCl in the stomach. Non-mast cell histamine occurs in gastric mucosa, possibly in cells called ‘histaminocytes’; situated close to the parietal cells, and has high turnover rate. It is released locally under the influence of all stimuli that evoke gastric secretion (feeding, vagal stimulation, cholinergic drugs and gastrin) and activates the proton pump (H+K+ ATPase) through H₂ receptors.

H₂ blockers not only suppress acid secretion induced by histamine but also markedly diminish that in response to ACh and gastrin. By a mutually synergistic interaction the three secretagogues amplify responses to each other with histamine playing the dominant role. As such, antimuscarinic drugs dampen the response to histamine and gastrin also. All three secretagogues activate the same proton pump (H+K+ATPase) in the parietal cell membrane, but through their own receptors.

Allergic Phenomena

Mediation of hypersensitivity reactions has been the first role ascribed to histamine. However, histamine is only one of the mediators of such phenomena. Released from mast cells following AG : AB reaction on their surface (involving IgE type of reaginic antibodies;) in immediate type of hypersensitivity reactions, histamine is causative in urticaria, angioedema, bronchoconstriction and anaphylactic shock. The H₁ antagonists are effective in controlling these manifestations to a considerable extent, except asthma and to a lesser extent anaphylactic fall in BP in which leukotrienes (especially LTD₄) and PAF appear to be more important. Histamine is not involved in delayed or retarded type of allergic reactions.

As Transmitter

Histamine is believed to be the afferent transmitter which initiates the sensation of itch and pain at sensory nerve endings.

Nonmast cell histamine occurs in brain, especially hypothalamus and midbrain. It is involved in maintaining wakefulness; H₁ antihistaminics owe their sedative action to blockade of this function. In the brain H₁ agonism suppresses appetite; certain H₁ antagonists stimulate appetite. Histamine also appears to act as a transmitter regulating body temperature, cardiovascular function, thirst, hormone release from anterior pituitary and possibly other functions.

Inflammation

Histamine has been implicated as a mediator of vasodilatation and other changes that occur during inflammation. It promotes adhesion of leukocytes to vascular endothelium by expressing adhesion molecule Pselectin on endothelial cell surface, sequestrating leukocytes at the inflammatory site. It may also regulate microcirculation according to local needs.

Tissue Growth And Repair

Because growing and regenerating tissues contain high concentrations of histamine, it has been suggested to play an essential role in the process of growth and repair.

Headache

Histamine has been implicated in certain vascular headaches, but there is no conclusive evidence.