In: Chemistry
Identify the two best characterized endocannabinoids (AEA and 2AG) and describe how they modulate neuorotransmitter release (retrograde).
** Needs to be a full paragraph, please do not answer unless you can do so fully**
Endocannabinoids are produced on demand either by activity-dependent or receptor-stimulated cleavage of membrane phospholipid precursors. Endocannabinoids can be released immediately from cells after their production since they are highly lipophilic and thus are poorly suited for storage.Different enzymes are implicated in the synthesis of AEA and 2-AG. AEA biosynthesis was originally believed to occur from enzymatic cleavage of a phospholipid precursor, N-arachidonoyl-phosphatidylethanolamine (NAPE). NAPE is synthesized by the enzymatic transfer of arachidonic acid in the sn-1 position of a phosphatidylcholine to the amide group of a phosphatidylethanolamine under the supervision of the calcium-independent N-acyl-transferase (NAT). First, the 2-AG precursor diacylglycerol (DAG) is formed from enzymatic cleavage of membrane phospholipid precursors by the enzyme phospholipase C (PLC.).2-AG is known to activate both CB1 and CB2 receptors.This compound is found in the brain in concentrations 170-fold higher than those of anandamide.In addition to activating metabotropic CB1 receptors, AEA can also activate ionotropic TRPV1 receptors as an endovanilloid. TRPV1 receptors are expressed in nociceptive sensory neurons and can detect/respond to noxious mechanical, thermal (i.e. heat) and chemical stimuli.