title: The evolution and comparative neurobiology of endocannabinoid signalling.
abstract: 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.
authors.affiliation: School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK. m.r.elphick@qmul.ac.uk
authors.forename: Maurice R
authors.initials: MR
authors.lastname: Elphick
mesh_terms: D000818:Animals; D005075:Biological Evolution; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002352:Carrier Proteins / Q000145:classification / Q000378:metabolism; D063388:Endocannabinoids / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D060588:LIM Domain Proteins / Q000145:classification / Q000378:metabolism; D007858:Learning / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D009446:Neurobiology / Q000379:methods; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010802:Phylogeny; D017729:Presynaptic Terminals; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C486181:CRIP1 protein, human; D002352:Carrier Proteins; D063388:Endocannabinoids; D060588:LIM Domain Proteins; D018377:Neurotransmitter Agents; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2