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’;
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.
Related Topics
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