Elphick_2012_Philos.Trans.R.Soc.Lond.B.Biol.Sci_367_3201

CB(1 and CB(2)-type cannabinoid receptors mediate effects of the endocannabinoids 2-arachidonoylglycerol 2-AG and anandamide in mammals In canonical endocannabinoid-mediated synaptic plasticity 2-AG is generated postsynaptically by diacylglycerol lipase alpha and acts via presynaptic CB(1)-type cannabinoid receptors to inhibit neurotransmitter release Electrophysiological studies on lampreys indicate that this retrograde signalling mechanism occurs throughout the vertebrates whereas system-level studies point to conserved roles for endocannabinoid signalling in neural mechanisms of learning and control of locomotor activity and feeding CB(1)/CB(2)-type receptors originated in a common ancestor of extant chordates and in the sea squirt Ciona intestinalis a CB(1)/CB(2)-type receptor is targeted to axons indicative of an ancient role for cannabinoid receptors as axonal regulators of neuronal signalling Although CB(1)/CB(2)-type receptors are unique to chordates enzymes involved in biosynthesis/inactivation of endocannabinoids occur throughout the animal kingdom Accordingly non-CB(1)/CB(2)-mediated mechanisms of endocannabinoid signalling have been postulated For example there is evidence that 2-AG mediates retrograde signalling at synapses in the nervous system of the leech Hirudo medicinalis by activating presynaptic transient receptor potential vanilloid-type ion channels Thus postsynaptic synthesis of 2-AG or anandamide may be a phylogenetically widespread phenomenon and a variety of proteins may have evolved as presynaptic or postsynaptic receptors for endocannabinoids.