Histamine Flashcards
Histidine
Non-toxic form; used by the body to make histamine (amino acid)
Histamine
Toxic form; hydrophobic & highly charged (pos.).. chemical found in body cell’s that causes symptoms of allergies (amine)
Histidine Decarboxylase (HDC)
Removes CO2 from Histidine to convert it into Histamine; “decarboxylation”
Production of Histamine
HDC removes CO2 from Histidine to turn it into Histamine
Packaging of Histamine
-ATPase pumps protons into granule
-VMAT2 exchanges protons in the granule with histamine in the cytosol (1 for 1 exchange), creating a proton motive force
Heparin
Release of histamine
- Translocation
- Docking
- Fusion
Translocation
-Granule filled with histamine in the cell
-VAMP attached to vesicle membrane
-SNAP attaches to cell membrane
Docking to fusion
-Vesicle membrane fuses with the cell membrane ONLY upon stimuli
(docking- action of coming together)
-VAMP and SNAP attach, opening the granule, allowing histamine to flood out of it into the blood (degranulation)
(fusion- action of histamine actually coming out)
Histamine as a neurotransmitter vs. endocrine hormone
If histamine is acting as a neurotransmitter, then it does not function endocrine style in the blood, it goes to the post synaptic cell
Possible stimuli to vesicle membrane fusion with cell membrane
-increase intracellular calcium
-chemical: venoms, detergent
-physical: injury, heat, UV
-antigens (aka toxic substances) (clinically most important)
Mast cell degranulation
-Histamine along with other substances flooding out of the granule
-It’s usually not just histamine in the granule/cell, there are other molecules present such as serotin
Histamine primary receptor response (H1)
-Found/expressed in smooth muscle, endothelium, brain, GI tract (food), mast cells
(NOT ONLY LOCATION, ITS THE PRIMARY RECEPTOR IN THE FOLLOWING REGIONS)
-increases IP3, diacylglycerol (DAG), intracellular Ca++
(DONE BY SECONDARY MESSENGER)
Histamine primary receptor response (H2)
-Found/expressed in gastric mucosa, brain, cardiac muscle, mast cells
(NOT ONLY LOCATION, ITS THE PRIMARY RECEPTOR IN THE FOLLOWING REGIONS)
-Increase cAMP and Ca 2+
(DONE BY SECONDARY MESSENGER)
THE MAIN BITCH
Histamine primary receptor response (H3)
-Found/expressed brain, neutron
(NOT ONLY LOCATION, ITS THE PRIMARY RECEPTOR IN THE FOLLOWING REGIONS)
-Decrease cAMP, inhibition of Ca 2+ channels
(DONE BY SECONDARY MESSENGER)
Histamine primary receptor (H4)
-Found/expressed in immune cells (eosinophils, neutrophils, T cells)
(NOT ONLY LOCATION, ITS THE PRIMARY RECEPTOR IN THE FOLLOWING REGIONS)
-Decreases cAMP, increases Ca 2+
(DONE BY SECONDARY MESSENGER)
Histamine primary receptors are…
7-transmembrane receptors aka- GPCRs (G protein-coupled receptors)
Termination of histamine
-Enzymatic degredation converts histamine into in/less active metabolites (major)
-uptake into cells (minor)
-receptor desensitization (minor)
Diamine Oxidase (DAO)
-found in intestines, kidneys, placenta
-deals with ezymatic degradation in extracellular histamine
-breaks down histamine into conjugates with ribose phosphates
Histamine Methyltransferase (HMT) (HNMT)
-found in kidney, liver, colon, pancreas, central nervous system (CNS)
-deals with intracellular histamine
-breaks histamine into N-methylhistamine oxidase
ECL- like Cell
secretes histamine:
-promotes parietal cell
-stimulates gastric acid (HCL) secretion
Histamine intolerance
-defined as the intolerance of histamine ingested with food
This happens when:
-ineffective DAO (some drugs inhibit DAO), not enough histamine is broken down
-too much histamine
Histamine receptor antagonist
-benadryl
-zantac
-claritin
-gravol
Histamine containing food
-fish: tuna fish, mackerel and anchovy (scombroid fish, scombrotoxin)
-cheese: emmental, Camembert and roquefort
-hard cured sausage: salami and raw ham
-vegetable: sauerkraut
-alcoholic beverages: red wine
H1 secondary messenger
PLC (Phospholipase C)
H2 secondary messenger
AC (adenylate cyclase)
H3 is an example of…
physiological antagonism
H1 response
-allergic conditions
-smooth muscle contraction
-vasodilation
-increase in vascular permeability
H2 response
-gastric acid secretion of HCL
-bicarbonate secretion
H3 response
-CNS disorders
-Release of neurotransmitter
-inhibition of gastric acid
H4 response
-immune system and inflammatory conditions
Histamine pathophysiological roles
-allergy and anaphylaxis
-food intolerance
-asthma
-motion sickness
-ulcers + gerd
-pain + itch
-narcolepsy
-scombrotoxic fish poisoning
What can histamine be packaged into
-mast cells: all over the body - lungs, gitract, skin
-ECL cells: gastric mucosa
-Basophics: white blood cells (WBCs)- all over body
-neurons
Histamine effects: humans
IN ORDER
-diarrhea
-flatulence
-sneezing
-runny nose
-headache
-itching
-itching and redness of eyes
Commonly used over-the-counter drugs
(histamine receptor antagonist)
-benadryl
-maxium strength zantac
-gravol
-claritin
Sir Henry Hallet Dale (1875-1968)
-discovered the biological implications of histamine
-mentioned the fact that histamine could play role in allergies
Histamine structure
primary amine, contains an imidazole ring and side chain
What is released from mast cells
Immediate: histamine, serotonin
Delayed: leukotrienes
