Histamine

What is histamine?

Histamine is an endogenous substance that exerts its

effects on many tissues & organs.
It is also called an autacoid i.e. a molecule which is
secreted locally to increase or decrease the activity of
nearby cells
Found in most mammalian tissue.
conc in plasma & other body fluids.
Significant amount in CSF.
Involved in local immune responses.
Regulate physiological functions in gut.
Acts as a neurotransmitter.
Because of its many physiological effects, drug that
inhibit its release or actions have therapeutic value

Synthesis & Storage

Produced locally by mast cells & basophils found in
nearby connective tissue.
Synthesized by decarboxylation of the amino acid
histadine by the enzyme histidine decarboxylase
After synthesis it is stored in secretory granules as
an inactive complex or is rapidly inactivated.
High conc in tissue containing large no. of mast
cells. Eg. Skin, bronchial tree mucosa, intestinal
mucosa.
Also present in neurons as neurotransmitter.

Physiological Effects
Plays central role in hypersensitivity & allergic
reactions.
Has important physiological roles.
Mediates diverse group of processes ranging from
vaso- dilation to gastric secretion.
Direct positive inotropic & chronotropic effects on
heart.
Contraction of bronchiolar smooth muscle.
Responsible for regulation of BP, body temperature,
fluid homeostasis & pain sensation.
Modulates neurotransmitter release.

Major Physiologic Actions of

TISSUE
EFFECTHistamine
OF
CLINICAL
RECEPTOR
HISTAMINE

PRESENTATION

SUBTYPE

Lung

Bronchoconstriction Asthma-like symptoms H1

Vascular smooth
muscle

Postcapillary
venule dilation,
Terminal arteriole
dilation,
Venoconstriction

Erythema

H1

Vascular
endothelium

Contraction &
separation of
endothelial cells

Edema, wheal
response

H1

Peripheral
nerves

Sensitization of
afferent nerve
terminals

Itchiness, pain

H1

Heart

Minor heart rate

& contractility

Minor

H2

Stomach

gastric acid
secretion

Peptic ulcer, heartburn H2

CNS

Neurotransmitter

Circadian rhythms,
wakefulness

H3

Mechanism of Action
Histamine acts by combining with cellular
histamine receptors.
4 types of receptors have been discovered.
H1, H2, H3, H4 receptors
The pharmacologic actions of histamine depend
on the tissue & type of receptors present at the
area of release

Type

Location

Function

H1
Found on
Receptor smooth muscle,
endothelium &
CNS tissue.
Primary
receptors
involved in
allergic rhinitis &
motion sickness.

Causes
vasodilation,
bronchial smooth
muscle
contraction,
separation of
endothelial cells
(hives), pain &
itching.

H2
Located on
Receptor parietal cells.

Primarily
stimulate gastric
acid secretion.

H3
Located in brain, Decreased
Receptor autonomic nerve neurotransmitter
endings, heart.
release.
H4
Found in bone
Receptor marrow, brain,
spleen, colon.

Unknown role.

Histamine Release From Mast Cells

A. Antigen- mediated histamine release.

Specific antigen-antibody interaction

degranulation of mast cells & basophils
release of histamine
Allergens are the most frequent cause.
Certain drugs esp. high molecular- wt molecules also caused
sensitization & degranulation of mast cells on subsequent drug
exposure.

B. Non antigen- mediated histamine release.

Do not require prior sensitization.

Drugs, high molecular wt proteins, venoms & others.
damage or disrupt cell membranesrelease of histamine.
Eg. Morphine, codeine, radiocontrast media.
Cytotoxics cause disruption of cell membranerelease of
histamine

Antigen Mediated Histamine

Release

Pathophysiology of Allergic Reaction

In a localised allergic reaction , an allergen (antigen) first

penetrates the epithelial surface (e.g. skin, nasal mucosa).
The allergen can also be delivered systemically, as in the case of
allergic response to penicillin.
The allergen will stimulates the production of IgE antibodies that
are specific for that allergen
The IgE then binds to receptors on mast cells & basophils, in a
process known as sensitization.
Once immune cells are sensitized, they can detect & respond
rapidly to a subsequent exposure to the same allergen.
Upon such a exposure, the allergen binds to & cross-links the
IgE/receptor complexs, triggering cell degranulation
Histamine released by mast cells & basophils binds to H1
receptors on vascular smooth muscle cells & vascular endothelial
cells.
Stimulation of H1 receptors causes blood vessel dilation &
increase vascular permeability

Symptoms Associated With Histamine

Release From Mast Cells
Mild cutaneous release : erythema, urticaria
and/or itching
Moderate Release : skin reactions, tachycardia,
moderate hypotension, respiratory distress
Severe Release (anaphylaxis) : severe
hypotension,
ventricular fibrillation, cardiac arrest, respiratory
arrest
due to severe bronchoconstriction & epiglotal
swelling