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    Histamine: Dr. Anil Kumar Saxena

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    Luqman Al-Bashir Fauzi
    Histamine is an autacoid that is synthesized from the amino acid histidine and stored in mast cells and basophils. Upon release, it acts as a mediator of inflammatory processes and regulates gastric acid secretion and neurotransmission. It binds to H1, H2, and H3 receptors and has various effects, including vasodilation, increased vascular permeability, smooth muscle contraction, and stimulation of gastric acid secretion. While it has no direct therapeutic uses, understanding its roles is important for treating conditions influenced by its actions such as allergies and gastric disorders.

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    Histamine: Dr. Anil Kumar Saxena

    Uploaded by

    Luqman Al-Bashir Fauzi
    66 views17 pages
    Histamine is an autacoid that is synthesized from the amino acid histidine and stored in mast cells and basophils. Upon release, it acts as a mediator of inflammatory processes and regulates gastric acid secretion and neurotransmission. It binds to H1, H2, and H3 receptors and has various effects, including vasodilation, increased vascular permeability, smooth muscle contraction, and stimulation of gastric acid secretion. While it has no direct therapeutic uses, understanding its roles is important for treating conditions influenced by its actions such as allergies and gastric disorders.

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    Histamine

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    Histamine is an autacoid that is synthesized from the amino acid histidine and stored in mast cells and basophils. Upon release, it acts as a mediator of inflammatory processes and regulates gastric acid secretion and neurotransmission. It binds to H1, H2, and H3 receptors and has various effects, including vasodilation, increased vascular permeability, smooth muscle contraction, and stimulation of gastric acid secretion. While it has no direct therapeutic uses, understanding its roles is important for treating conditions influenced by its actions such as allergies and gastric disorders.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    66 views17 pages

    Histamine: Dr. Anil Kumar Saxena

    Uploaded by

    Luqman Al-Bashir Fauzi
    Histamine is an autacoid that is synthesized from the amino acid histidine and stored in mast cells and basophils. Upon release, it acts as a mediator of inflammatory processes and regulates gastric acid secretion and neurotransmission. It binds to H1, H2, and H3 receptors and has various effects, including vasodilation, increased vascular permeability, smooth muscle contraction, and stimulation of gastric acid secretion. While it has no direct therapeutic uses, understanding its roles is important for treating conditions influenced by its actions such as allergies and gastric disorders.

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    HISTAMINE

    Dr. Anil Kumar Saxena


    AUTACOIDS

    These are substances produced by wide variety of


    cells in the body, having intense biological activity,
    but generally act locally (with exception of
    ‘anaphylactic shock’) at the site of synthesis &
    release.
    Also known as local hormones but some
    differences from hormones.
    The classical autacoids are: Histamine, 5-HT,
    Prostaglandins, Leucotrienes, Platelet activating
    factor, Plasma kinins, Angiotensin.
    HISTAMINE

    Histamine (histos = tissue) is a biogenic amine


    found in many tissues.
    It is an autacoid; that is a molecule secreted locally
    to increase or decrease the functional activity of
    nearby cells.
    Histamine is a major mediator of inflammatory
    processes; it also has a significant role in regulating
    gastric acid secretion & in neurotransmission.
     Histamine is present mostly within storage
    granules of mast cells.

     Tissues rich in histamine are skin, gastric &


    intestinal mucosa, lungs, liver & placenta.

     Non-mast cell histamine occurs in brain,


    epidermis, gastric mucosa & growing regions.

     Histamine is also present in blood, most body


    secretions, venoms & pathological fluids.
    Histamine Synthesis, Storage & Release

    Histamine is synthesized from the amino acid L-


    histidine.
    The enzyme histidine decarboxylase catalyzes the
    decarboxylation of histidine to produce histamine.

    Histidine

    Decarboxylation L-histidine decarboxylase

    Histamine
    The synthesis of histamine occurs mainly in:
    • Mast cells,
    •Basophils,
    • Enterochromaffin-like cells (ECL cells) in the
    gastric mucosa,
    • Certain neurons that use histamine as a
    neurotransmitter.

    Once histamine is released, liver rapidly degrade it


    into inert metabolites.
     A major metabolite of histamine, imidazole-
    acetic- acid, can be measured in the urine & the
    level of this metabolite can be used to determine
    the amount of histamine that has been released
    systemically.

    Histamine Synthesis & Storage


    a) Slowly turning over pool
    b) Rapidly turning over pool

    a) Slowly turning over pool is located mainly in


    mast cells & basophils.
    In these inflammatory cells, histamine is stored in
    large granules & the release of histamine involves
    complete degranulation of these cells.
    Several weeks are required to replenish the stores
    of histamine after degranulation – that is why it is
    called slowly turning over pool.

    b) Rapidly turning over pool is located in gastric


    ECL cells & in histaminergic CNS neurons.
    These cells synthesize & release histamine as
    required for gastric acid secretion &
    neurotransmission.
    Unlike mast cells & basophils, ECL cells &
    histaminergic neurons do not store histamine.
    Production of histamine in these cells depends on
    physiologic stimuli. For ex, in the gut, histidine
    decarboxylase is activated after the ingestion of
    food.

    ACTIONS OF HISTAMINE
    1.Smooth muscle: Some smooth muscle fibers
    contract while others relax.
    • Bronchial smooth muscle - Contracts.
    •Terminal arterioles & post-capillary venules -
    Dilates
     Veins – Constrict.
     Other smooth muscle in the bowel, bladder, iris,
    & uterus – Constrict, but the effect is not
    significant.
     Vascular endothelium – Contraction, resulting in
    separation of these cells from one another. This
    allows escape of plasma proteins & fluid from
    post-capillary venules & thereby causing edema.
     Peripheral sensory nerve terminals: The
    sensation of itch & pain result from a direct
    depolarizing action of histamine on afferent nerve
    terminals. This effect is responsible for the pain &
    itch experienced after an insect bite or sting.
    The combined actions of histamine on vascular smooth
    muscle, vascular endothelial cells, & nerve terminals are
    responsible for the “wheal and flare” response noted
    following histamine release in the skin.

    Histamine causes “triple response” on intradermal inj.


    a) Red spot: intense capillary dilatation.
    b) Wheal: exudation of fluid from capillaries &
    venules.
    c) Flare: redness in the surrounding area due to
    arteriolar dilatation
    2. Heart: Minor increases in the force & rate of
    contraction.
    3. Stomach:
    •Histamine is a potent stimulator of acid secretion by
    parietal cells in the gastric mucosa.
    •Histamine is one of the three molecules that
    regulate acid secretion in the stomach, the others
    being gastrin & acetylcholine.
    •The primary role of histamine in the gastric mucosa
    is to potentiate gastrin-induced acid secretion.
    4. CNS:
    •Histamine also functions as a neurotransmitter in
    the CNS.
    •Both histaminergic neurons with histidine
    decarboxylase & histamine receptors are present in
    the hypothalamus with diffuse projections
    throughout the brain & spinal cord.
    •Functions of histamine in the CNS are not well
    understood. It is believed that it is involved in the
    maintenance of wakefulness & to act as an appetite
    suppressant.
    HISTAMINE RECEPTORS: H1, H2, H3

    H1

    •Involved in inflammation & allergic reactions.


    •Present on vascular endothelial cells & smooth
    muscle cells.
    •Stimulation cause:

    1. Edema
    2. Bronchoconstriction
    3. Sensitization of primary afferent
    nerve terminals, depending on the tissue
    type
    • H1 receptor is also present on the pre-synaptic
    membranes of histaminergic neurons in the
    hypothalamus, where it acts as an autoreceptor to
    inhibit further release of histamine.
    • These neurons may be involved in the control of
    circadian rhythm & wakefulness.

    H2 receptor
    • Major function is to mediate gastric acid secretion
    in the stomach.
    • Present on parietal cells in the gastric mucosa.
    • H2 receptors are also present on cardiac muscle
    cells, on some immune cells, & on certain
    presynaptic neuronal membranes.

    H3 receptor
    • Currently little is known about their actions.
    • They are present on presynaptic nerve terminals
    in the CNS, where they limit the release of
    histamine from histaminergic neurons.
    • They have also been shown to limit histaminergic
    actions in gastric mucosa & bronchial smooth
    muscle.
    Clinical Uses

    Histamine has no therapeutic use.

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