AB2, L19: Inflammatory Mediators 2

Given definition, answer w/ term

Histamine

• Definition: Biogenic amine linked to 23 different physiological functions

• Leads to:

  • Smooth muscle contraction of bronchi, gut, and large vessels

  • Smooth muscle relaxation in small arterioles, which leads to a significant decrease in blood pressure

  • Increased vascular permeability, which leads to edema

  • Increased secretion of gastric acid

• Functions:

  • Physiological:

    • Gastric acid secretion

    • Neurotransmission

  • Acute inflammation:

    • Anaphylaxis

    • Allergies

Granules in mast cells, platelets, histaminergic neurons, and enterochromaffin cells

List the 4 locations of histamine storage

• Primary location: _______ in _______ cells

• Also located in: _______, _______ neurons, and _______ cells

H1, H2, H3, and H4

Histamine Receptors vary in expression, signaling, function, and histamine binding ability

• Pleiotropic effects of histamine are mediated by which 4 receptors?

Anaphylaxis, allergies, and mediator of pruritus

Inflammatory Effects of Histamine

• Acute inflammation:

  • _______

  • _______

• Mediator of _______ (in conjunction with Prostaglandin E₂)

Pruritus

• Definition: Unpleasant cutaneous sensation leading to the desire to scratch

• Mediator: Histamine

Anaphylaxis

• Definition: An immediate and potentially fatal systemic reaction

• Mediator: Histamine via H1, H2, and H3 receptors

• Cause: IgE mediated degranulation of mast cells and basophils leads to increased vascular permeability and vasodilation

Histamine antagonists

Histamine Pharmacology:

• Definition: Bind, but do not activate, histamine receptors. This drug does not inhibit histamine release

• Effectivity:

  • More effective if given pre-emptively

  • Well absorbed in monogastrics, poorly absorbed in ruminants

H1R antagonists

1 of the 4 Types of Histamine Antagonists:

• Treat: Allergic disorders in dogs and humans

• Notable Features:

  • Variable responses in dogs

  • Cats relatively sensitive

H2R antagonists

1 of the 4 Types of Histamine Antagonists:

• Treat: Peptic ulcers and GI bleeding in dogs and cats

• Examples: Ranitidine

H3R antagonists

1 of the 4 Types of Histamine Antagonists:

• Treat:

  • Metabolic disorders in dogs and cats

  • Sleep and wakefulness disorders, attention disorders, obesity, and Alzheimer’s disease in humans

• Primarily used in research, not many clinical veterinary applications

H4R antagonists

1 of the 4 Types of Histamine Antagonists:

• Treat:

  • IBD

  • Asthma

  • Pruritus

• Primarily used in research, not many clinical veterinary applications

Serotonin

Pharmacology:

• Function:

  • Neurotransmitter that regulates sleep and mood

  • Peripheral hormone that has a regulatory role in inflammation

• Clinical Importance:

  • SSRIs – used tp manage depression in people and behavioral issues like separation anxiety and noise phobia in dogs

Briefly describe the synthesis and transport of serotonin

(5-HT) and its release in response to stimuli

Histamine metabolism

Histamine synthesis

Histamine Synthesis:

Synthesized slowly, and released instantly

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