Endocannabinoids
Lipids Signaling

Author: Francesco Licciardi
Date: 18/03/2009

Description

Endocannabinoids are the cannabinoids endogenously produced by animals.

The identification of receptors for cannabinoids allowed a search for endogenous ligands that was rewarded by the discovery that an arachidonic acid derivative, arachidonoyl ethanolamide, bound with high affinity to the CB1 receptor.

This compound, which is called anandamide (from the Sanskrit ‘a-nanda’ : meaning, ‘happiness, joy, enjoyment, sensual pleasure ’) had pharmacological and behavioural effects very similar to D9-tetrahydrocannabinol.

Cannabinoids metabolism

The synthetic pathway involves breaking down the membrane phospholipid precursor, N-arachidonoyl phosphatidylethanolamine, to yield anandamide by a phospholipase enzyme.

Inactivation of anandamide is by re-uptake through a specific carrier followed by hydrolysis by fatty acid amide hydrolase.
The precursor of anandamide (N-arachidonoyl phosphatidylethanolamine) is synthesised by Ca2+ - dependent trans-acylation of phosphatidylethanolamine and the arachidonate is thought to be donated by 1,2-sn-diarachidonoyl phosphatidylcholine.

Two other endogenous compounds, 2-arachidonoylglycerol(2-AG) and the structurally related 2-arachidonoylglyceryl ether also been found to bind to cannabinoid sites.

2-AG has been proposed as being the endogenous agonist for the CB2 receptor and is synthetised from the signalling molecule 1,2-sn-diacylglycerol (DAG) by DAG lipase.
Unlike anandamide, there does not appear to be a facilitated transport system for 2-AG.

There are several other putative endocannabinoids described in the literature.
These include

  • N-palmitoylethanolamide (also proposed as a selective endogenous CB2 receptor agonist),
  • Docosatetraenylethanolamide (CB1 agonist),
  • N-arachidonoyldopamine (a CB1 receptor selective ligand)
  • Virodhamine (O-arachidonoylethanolamine; described as an endogenous CB1 receptor partial agonist and CB2 receptor agonist).

Interestingly, the arachidonic acid derivative N-arachidonoylglycine acts to suppress pain, which is often associated with agonist activity at CB1 receptors, but has no affinity for this cannabinoid receptor.

Regulation of Cannabinoids metabolism

That anandamide might be an endogenous mediator is supported by the observation that depolarised rat brain neurons in culture produced it.

Per maggiori informazioni Wikipedia

Per informazioni sui recettori
Per informazioni sui esocannabinoidi

Bibliography

C.ROBIN HILEY and WILLIAM R.FORD (2004) Cannabinoid pharmacology in the cardiovascular system: potential protective mechanisms through lipid signalling
Biol.Rev., 79 pp 187-205

MANUEL GUZMAN. CRISTINA SANCHEZ, ISMAEL GALVE-ROPERH (2002) Cannabinoids and cell fate
Pharmacology & therapeutics 95 pp 175-184

Francesco Licciardi e Matteo Manfredi

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