Histamine Release and Receptors
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Questions and Answers

What initiates the formation of IgE upon first exposure to an antigen?

  • Chemical displacement of histamine
  • Formation of IgE antibodies (correct)
  • Degranulation of mast cells
  • Binding of histamine to mast cells

    • Which of the following is required for immunological release of histamine?

  • Amines such as tubocurarine
  • Histamine receptors H1 and H2
  • Presence of toxins
  • Energy and calcium (correct)

    • Which histamine receptor subtype is primarily involved in increasing cAMP levels?

  • H4
  • H1
  • H2 (correct)
  • H3

    • What distinguishes chemical and mechanical release of histamine from immunological release?

    <p>It involves the displacement of histamine without mast cell injury</p> Signup and view all the answers

    What effect does released histamine exert via H2 receptors on mast cells?

    <p>Negative feedback mediated by cAMP</p> Signup and view all the answers

    Which of the following is NOT a distribution site for H1 receptors?

    <p>Gastric mucosa</p> Signup and view all the answers

    What is one effect of serotonin (5-HT) on large blood vessels?

    <p>It causes significant contractions in vascular smooth muscle cells.</p> Signup and view all the answers

    Which type of receptor, among the histamine receptors, is associated with presynaptic locations in the CNS?

    <p>H3</p> Signup and view all the answers

    In the context of serotonin's actions on platelets, how does it contribute to platelet aggregation?

    <p>By binding to specific receptors that enhance aggregation.</p> Signup and view all the answers

    What is the mechanism of action for histamine released from mast cells?

    <p>It activates various second messenger pathways depending on receptor subtype</p> Signup and view all the answers

    What role does serotonin (5-HT) play in the central nervous system (CNS)?

    <p>It can induce hallucinations and affects mood and anxiety.</p> Signup and view all the answers

    How does serotonin affect small blood vessels?

    <p>It leads to dilation mainly through the action of nitric oxide.</p> Signup and view all the answers

    What is one consequence of injecting serotonin (5-HT) intravenously?

    <p>It leads to an initial increase followed by a drop in blood pressure.</p> Signup and view all the answers

    Which receptor is primarily involved in the vasodilation effect of histamine on vascular smooth muscle?

    <p>H2 receptor</p> Signup and view all the answers

    What effect does histamine have on cardiac function?

    <p>Increases heart rate</p> Signup and view all the answers

    In asthmatic patients, histamine typically causes which of the following effects?

    <p>Severe bronchoconstriction</p> Signup and view all the answers

    Histamine acts on what type of cells in the gastric system to increase acid secretion?

    <p>Parietal cells</p> Signup and view all the answers

    Which effect of histamine can lead to edema in tissues?

    <p>Increased capillary permeability</p> Signup and view all the answers

    What adverse effect can occur in the gastrointestinal tract due to histamine's action?

    <p>Severe abdominal cramps</p> Signup and view all the answers

    What sensation does histamine cause in the epidermis?

    <p>Itching</p> Signup and view all the answers

    Which of the following describes the mechanism of histamine's direct action on vascular smooth muscle?

    <p>Release of intracellular calcium</p> Signup and view all the answers

    What is the primary purpose of Pizotifen in migraine treatment?

    <p>Prophylactic prevention of migraine attacks</p> Signup and view all the answers

    Which receptor is primarily involved in the emesis process?

    <p>5-HT3 receptors</p> Signup and view all the answers

    What is the mechanism of action for SSRIs in treating depression?

    <p>Blocking serotonin transporter (SERT)</p> Signup and view all the answers

    Which of the following conditions is NOT typically treated with 5-HT3 antagonists?

    <p>Chronic migraines</p> Signup and view all the answers

    What is a common underlying theory connecting serotonin levels to depression?

    <p>Depression is linked to a deficit of monoamine neurotransmitters</p> Signup and view all the answers

    What is a common side effect associated with 1st generation H1 antagonists?

    <p>Drowsiness</p> Signup and view all the answers

    Which mechanism primarily accounts for the anti-emetic effects of promethazine?

    <p>Anti-dopaminergic action</p> Signup and view all the answers

    Where is the highest concentration of serotonin (5-HT) found in the body?

    <p>Enterochromaffin cells</p> Signup and view all the answers

    Which 5-HT receptor subtype is primarily responsible for the inhibition of serotonin release?

    <p>5-HT1B</p> Signup and view all the answers

    What action does 5-HT have on the gastrointestinal tract?

    <p>Facilitates peristalsis</p> Signup and view all the answers

    What enzyme is primarily responsible for the degradation of serotonin (5-HT)?

    <p>Monoamine oxidase A</p> Signup and view all the answers

    Which of the following 1st generation antihistamines primarily promotes sedation?

    <p>Promethazine</p> Signup and view all the answers

    Which receptor subtype is a ligand-gated cation channel among 5-HT receptors?

    <p>5-HT3</p> Signup and view all the answers

    What physiological effect does activation of the vomit center by 5-HT lead to?

    <p>Nausea and emesis</p> Signup and view all the answers

    Which compound is used as an anxiolytic through partial agonism at 5-HT receptors?

    <p>Buspirone</p> Signup and view all the answers

    Study Notes

    Histamine Release

    • Immunological Release:

      • First exposure to an antigen results in the formation of IgE, which binds to mast cells.
      • Second exposure triggers explosive degranulation, releasing histamine.
      • This process requires calcium and energy.
      • IgG and IgM can also stimulate histamine release from mast cells.
      • Released histamine exerts negative feedback via H2 receptors on mast cells in the skin and blood, but not the lungs.

    • Chemical and Mechanical Release:

      • Certain amines, including drugs like morphine and tubocurarine, can displace histamine from its bound form within cells.
      • This process doesn't require energy and is not associated with mast cell injury or explosive degranulation.

    Histamine Receptors

    • There are four subtypes of histamine receptors: H1, H2, H3, and H4.
    • All histamine receptors are G protein-coupled receptors (GPCRs).
    • H1 receptors are primarily found in smooth muscle (vascular and bronchial), endothelial cells, the CNS, and other cell types.
    • H2 receptors are mainly located in the gastric mucosa, parietal cells, cardiac muscle, smooth muscle, mast cells, the CNS, and other cell types.
    • H3 receptors are found in the CNS (presynaptic) and other cell types.
    • H4 receptors are found in cells of hematopoietic origin.

    Histamine Actions

    • Blood Vessels:

      • Histamine causes vasodilation via H1 receptors on vascular endothelium, leading to nitric oxide (NO) release.
      • It also directly dilates vascular smooth muscle through H2 receptors.
      • Histamine increases capillary permeability via H1 receptors on endothelial cells, causing fluid and plasma protein leakage into the extracellular space.

    • Heart:

      • Histamine affects cardiac contractility and electrical activity.
      • It increases heart rate and force of contraction through H2 receptors.

    • Gastrointestinal Tract:

      • Histamine contracts GI smooth muscle, potentially causing abdominal cramps and diarrhea.

    • Airways:

      • Histamine constricts bronchial smooth muscle primarily through H1 receptors by increasing calcium levels.

    • Skin:

      • Histamine causes itchiness and local inflammatory responses.

    • Sensory Nerves:

      • Histamine stimulates sensory nerve endings, contributing to itching, sneezing, and other sensory effects.

    Histamine Antagonists (H1)

    • First-generation antihistamines are not selective for histamine receptors and can have anti-muscarinic and anti-dopaminergic effects.
    • Examples include diphenhydramine, chlorpheniramine, and promethazine.
    • Side effects include dry mouth, blurred vision, urinary retention, constipation, and marked sedation.

    Other Uses of H1 Antagonists

    • Anti-emetic: Promethazine can be used for motion sickness, morning sickness, and vertigo.
    • Sedative: First-generation antihistamines can be used as sleep aids.

    H2 Receptor Antagonists

    • Pharmacology and Clinical Utility:
      • Primarily used to inhibit gastric acid secretion.
      • Helpful for gastrointestinal reflux or ulcers.
      • Examples: ranitidine and cimetidine.

    Serotonin (5-HT)

    • 5-HT is both a neurotransmitter and a local hormone.

    • Highest concentrations are found in the intestinal wall, blood platelets, and the central nervous system.

    • Synthesis: 5-HT is synthesized from the amino acid L-tryptophan in chromaffin cells and neurons.

    • Storage: 5-HT is stored in intracellular vesicles via vesicular transporters.

    • Uptake: Platelets and neurons utilize active transporters for 5-HT uptake.

    • Degradation: 5-HT is degraded primarily by monoamine oxidase A (MAO) followed by oxidation to 5-hydroxyindoleacetic acid (5-HIAA), which is excreted in the urine.

    5-HT Receptor Classification

    • There are 14 subtypes of 5-HT receptors divided into 7 classes (5-HT1-7).
    • All are GPCRs except 5-HT3, which is a ligand-gated cation channel.
    • Most 5-HT receptor agonists and antagonists are non-selective with respect to receptor subtypes, except for 5-HT3-selective agents.

    5-HT1 Receptors

    • 5-HT1A:

      • Location: CNS (presynaptic and postsynaptic neurons).
      • Effects: Activates presynaptic neurons to inhibit serotonin release, regulating mood, anxiety, and stress; partial agonists like buspirone are used as anxiolytics.

    • 5-HT1B and 5-HT1D:

      • Location: Presynaptic neurons in the CNS, smooth muscle of cranial blood vessels.
      • Effects: Inhibit serotonin release and cause vasoconstriction; triptans, which are 5HT-1B/1D agonists, are used for migraine treatment.

    Pharmacologic Actions of 5-HT

    • Gastrointestinal Tract Motility: 5-HT facilitates peristalsis, intestinal motility, and secretion by acting directly on smooth muscle and stimulating enteric nervous system ganglion cells.

    • Nausea and Emesis: 5-HT induces nausea and emesis through activation of brain regions that control vomiting, particularly via stimulation of the vomit center in the medulla and inputs from vagal sensory fibers in the GI tract.

    • Cardiovascular Effects:

      • Blood Vessels: 5-HT's effects on blood vessels depend on vessel size, location, and 5-HT receptor subtype; it typically constricts large vessels (arteries and veins) by acting directly on vascular smooth muscle cells and dilates small vessels by releasing nitric oxide (NO) and inhibiting norepinephrine release from sympathetic nerve terminals.
      • Platelets: 5-HT, stored and released by platelets after contact with injured endothelium, promotes platelet aggregation by binding to platelet 5HT2A receptors.

    • Peripheral Nervous System: 5-HT stimulates nociceptive sensory nerve endings, contributing to neurogenic inflammation.

    • Central Nervous System: 5-HT plays a role in various CNS-mediated events like migraine, stress, anxiety, mood, vomiting, and appetite. It can also induce hallucinations. Cellular effects in the CNS depend on the receptor subtype and can include post-synaptic excitation, inhibition, and pre-synaptic inhibition.

    5HT Receptor Antagonists as Antiemetics

    • Nausea and Vomiting: 5-HT release in the GI tract and CNS contributes to emesis, primarily mediated through 5HT3 receptors in the vomit center and peripheral neurons in the GI tract.

    • Clinical Implications: 5HT3 antagonists are effective antiemetic drugs, such as ondansetron and tropisetron, used for prevention of nausea and vomiting associated with post-surgical procedures, chemotherapy and radiation treatments.

    Depression and Serotonin

    • Monoamine Theory of Depression: Depression is linked to a deficit of monoamine neurotransmitters, including serotonin, in the limbic system.

    • Selective Serotonin Reuptake Inhibitors (SSRIs):

      • Mechanism: SSRIs block the serotonin transporter (SERT) to inhibit serotonin reuptake, enhancing serotonergic neurotransmission.
      • Uses: Treat depression and anxiety disorders.

    • 5-HT1A Receptor Partial Agonists:

      • Mechanism: These agonists act on presynaptic inhibitory 5-HT1A receptors, enhancing serotonergic activity.
      • Uses: Used for treatment of depression and anxiety.

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    Description

    Explore the mechanisms of histamine release in immunological and chemical contexts. Understand how IgE and certain drugs interact with mast cells and the role of different histamine receptors. This quiz covers the intricacies of histamine's effects on the body and its receptors.

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