Endocannabinoids Flashcards
Structure of endocannabinoids
Endocannabinoids are lipids in structure = hydrophobic but not so lipophilic that
they will constantly remain in the membrane
Have very different chemical structures compared to
phyto/synthetic cannabinoids but can share some
pharmacology
- Anandamide (AEA) is a partial agonist (shares this
property with THC) and 2-AG is full agonist
Biosynthesis of endocanabinoids
Synthesised from quite unusual lipids
Synthesis of anandamide:
- Start with small amount of phosphatidylethanolamine = converted by N-acyl
transferase into N-arachidonoyl PE
- N-arachidonoyl PE is then converted by Phospholipase D into Anandamide
- Increasing calcium levels will increase activity of phospholipase D
There are at least two pathways
which can produce 2-AG = 2-AG
found at much higher levels than
anandamide
Synthesis of 2-AG:
- Start with
phosphatidylinositol
(abundant in brain)
How are endocanabinoids produced
Not known as neurotransmitters
as they don’t get packaged and stored
Stimuli for de novo synthesis:
- From phospholipid-derived precursors
- Activation of GPCRs, PLC, increased intracellular Ca2+ concentration
Produced from and target tissues in:
- Neurones, cardiac myocytes, astrocytes, microglia, blood cells, vascular wall, gut
How are endocanbinoids detected
Not very easy to detect lipids so use liquid chromatography-mass spectrometry to
accurately identify the structure and concentration
- Tissue broken down and dissolved in organic solvent = forced into HPLC column =
separates lipids based on structure and physical properties
- Sent each individual molecule to mass spectrometer = bombarded with high
energy beam to be broken down into small components = detector identifies
mass of each component = put together to identify an overall structure
How are they degraded
Enzyme responsible for the breakdown of anandamide is FAAH = fatty acid amide
hydrolase (some NSAIDs inhibit FAAH)
Enzyme responsible for the breakdown of 2-AG is MGL = monoacyl glycerol lipase
