Histamine

Who discovered Histamine

Sir Henry Hallett Dale

Where is Histamine synthesized and how

• synthesized in the cytoplasm

• It is made from the amino acid L-Histadine

• with the help of decarboxylase to remove the COOH group

What cells are histamine stored in

• mast cells

• basophils

• ECL

• Neurons

Who provided the description of mast cells

Pau Ehrlich

How is histamine stored in Mast cells

in granules

Process of storing histamine in granules

• ATPase is present in the granules to transport protons into the granule

• This creates a proton motive force

• the protons can be exchanged for a hydrophilic cation

• The transporter is VMAT2

• VMAT2 takes protons out and puts in histamine

What causes degranulation

• Physical: injury, heat, x-ray, UV damage

• Chemical: snake venom, bee, drugs and detergeents

• Antigen

What is the process of vesicle fusion

1. Translocation- upon activation, the granules translocate

2. Docking- dock at the plasma membrane where the granule proteins and membrane proteins form a complex

3. Fusion- fusion allows granules to secrete their contents

H1 receptors

• smooth muscle and endothelium, brain

• Gq second messenger, increase IP3 and DAG

• cause allergy symptoms

H2 receptors

• Gastric mucosa, cardiac muscles, mast cells and brain

• Gs, increase cAMP increasing protein kinases

• Gastric acid secretion

H3 receptors

• presynaptic autoreceptors and heteroreceptors

  • brain, myenteric plexus, CNS

  • Gi, decrease cAMP, inhibit protein kinases

H4 receptors

• Eosinophils, neutrophils, mast cells

• pain and itching

• Gi, decrease cAMP

What enzymes cause the termination of Histamine

• Diamine Oxidase (extracellular)

• HNMT (intercellular)

What can Histamine cause

• Allergy and anaphylaxis

• Food intolerance

• ulcers and gastro-esophageal reflux disease

• Pain and itch

• Scombrotoxic fish poisoning

How are antigens stimulated

• During the first exposure, plasma cells produce IgE antibodies

• IgE molecules fix onto specfic IgE antibodies

• 2 exposure antigens cross link fixed IgE antibodies

• Perturbation leads to release

What is an antagonist

• a molecule which inhibits the receptor and doesn’t allow histamine to carry out its response