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.

Endocannabinoids in nervous system health and disease: the big picture in a nutshell

“…CB1, CB2) and proteins that regulate cannabinoid receptor activity. This volume begins with a chapter by Elphick [3], who takes us on an evolutionary tour of endocannabinoid signalling in the animal kingdom. This forms the basis of a presentation on selected examples of research on the neurophysiological roles of endocannabinoid signalling in non-mammalian animals.…”

The Endocannabinoid/Endovanilloid N-Arachidonoyl Dopamine (NADA) and Synthetic Cannabinoid WIN55,212-2 Abate the Inflammatory Activation of Human Endothelial Cells

“…N-Arachidonoylethanolamide (AEA; anandamide) and 2-arachidonoylglycerol (2-AG) are the two most thoroughly studied eCBs; however, other eCBs also exist, including 2-arachidonyl glycerol ether (Noladin ether), O-arachidonoylethanolamine (virodhamine), N-arachidonoyl glycine, and N-arachidonoyl dopamine (NADA) (1). Although the functions of AEA and 2-AG in neuronal synaptic plasticity have been substantially documented, the functions of these molecules outside the nervous system, and the roles of the other eCBs, are not as well understood (5)(6)(7)(8).…”

Pentylenetetrazol-induced seizure-like behavior and neural hyperactivity in the medicinal leech

“…PTZ-induced hyperactivity was prevented by co-treatment with the endocannabinoid 2-AG. As in the mammalian CNS, 2-AG is the most abundant endocannabinoid in the leech CNS and both 2-AG and anandamide are known to be present in other invertebrates (De Petrocellis et al 1999;Matias et al 2001;Lehtonen et al 2008;Elphick 2012). Endocannabinoids have been proposed as a potential therapeutic approach for treating epilepsy, presumably due to their ability to elicit persistent depression of glutamatergic synapses (Marsicano et al 2003;Katona and Freund 2008;Izzo et al 2009;Bhaskaran and Smith 2010;Zurolo et al 2010).…”

“…In the leech, 2-AG and the synthetic cannabinoid CP 55,940 have been observed to induce long-lasting depression in glutamatergic synapses utilizing cellular mechanisms that are remarkably similar to those responsible for endocannabinoid-dependent long-term depression (eCB-LTD) in the mammalian brain Burrell 2009, 2010;Yuan and Burrell 2010;Li and Burrell 2011;Katona and Freund 2012;Yuan and Burrell 2012). One difference is that the leech, like other protostomal invertebrates, lack orthologues to the mammalian CB1 and CB2 receptors (Elphick 2012). However, it has been known for some time that transient receptor potential vanilloid 1 (TRPV1) channels can also act as endocannabinoid receptors and can mediate some forms of eCB-LTD (Zygmunt et al 1999;Gibson et al 2008;Chavez et al 2010;Grueter et al 2010;Di Marzo and De Petrocellis 2012).…”