Histamine
The hormone/chemical transmitter histamine is a biogenic monoamine similar
to serotonin, epinephrine and norepinephrine. Chemically histamine is 2-(4-
imidazolyl)ethylamine and has the formula C5H9N3. It is found in plant and
animal tissue and released from mast cells as part of an allergic reaction. Use of
histamine in the body is not solely involved in allergic inflammatory response.
It is released in allergic reactions and causes widening of capillaries, decreased
blood pressure, increased release of gastric juice, fluid leakage forming itchy skin
and hives, and tightening of smooth muscles of the bronchial tube and uterus.
It stimulates gastric secretion and causes dilation of capillaries, constriction of
bronchial smooth muscle, and decreased blood pressure and plays a role in the
movement (chemotaxis) of white blood cells. It is hydrophilic and once formed is
either stored or rapidly inactivated.
Most tissue histamine is found in granules in mast cells or basophils and its release
is immunologic in function. Mast cells are especially numerous at sites of potential
injury such as the nose, mouth, and feet, internal body surfaces and blood vessels.
Basophils represent only 1% of circulating leukocytes. Like mast cells basophils
store histamine, they tend to appear in specific kinds of inflammatory reactions,
particularly those that cause allergic symptoms. Non-mast cell histamine is found
in several tissues, including the brain, where it functions in both neurotransmission
and regulation of brain blood flow and vascular permeability effects. Another
important site of histamine storage and release is the enterochromaffin-like (ECL)
cell of the stomach. ECL cells are a distinctive type of neuroendocrine cell underlying
the epithelium in the gastric mucosa, most prevalent in the acid-secreting regions
of the stomach. Together, histamine and gastrin are primary positive regulators of
hydrochloric acid secretion from the parietal cell.
The four types of histamine receptors each have a different mode of action:
H1 histamine receptor—found on smooth muscle, endothelium, and central
nervous system tissue; causes vasodilation, bronchoconstriction, smooth muscle
activation, and separation of endothelial cells (hives/bleeding from the pores), and
pain and itching due to insect stings; the primary receptors involved in allergic
symptoms and motion sickness. Initiates release of intracellular stores of Ca2+ and
opens voltage gated calcium channels.
H2 histamine receptor—located on parietal cells, which primarily regulate
gastric acid secretion. It is a potent stimulant of cAMP production. It instigates
the release of Ca2+ from intracellular stores and increases the intracellular Ca2+
concentrations.
H3 histamine receptor—The H3 receptor has been shown to presynaptically
inhibit the release of a number of other neurotransmitters including dopamine,
GABA, acetylcholine, noradrenaline, and serotonin. It leads to inhibition of the
formation of cAMP.