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The Phylogenetic Distribution and Evolutionary Origins of Endocannabinoid Signalling

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Cannabinoids

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 168))

Abstract

The endocannabinoid signalling system in mammals comprises several molecular components, including cannabinoid receptors (e.g. CB1, CB2), putative endogenous ligands for these receptors [e.g. anandamide, 2-arachidonoylglycerol (2-AG)] and enzymes involved in the biosynthesis and inactivation of anandamide (e.g. NAPE-PLD, FAAH) and 2-AG (e.g. DAG lipase, MGL). In this review we examine the occurrence of these molecules in non-mammalian organisms (in particular, animals and plants) by surveying published data and by basic local alignment search tool (BLAST) analysis of the GenBank database and of genomic sequence data from several vertebrate and invertebrate species. We conclude that the ability of cells to synthesise molecules that are categorised as “endocannabinoids” in mammals is an evolutionarily ancient phenomenon that may date back to the unicellular common ancestor of animals and plants. However, exploitation of these molecules for intercellular signalling may have occurred independently in different lineages during the evolution of the eukaryotes. The CB1- and CB2-type receptors that mediate effects of endocannabinoids in mammals occur throughout the vertebrates, and an orthologue of vertebrate cannabinoid receptors was recently identified in the deuterostomian invertebrate Ciona intestinalis (CiCBR). However, orthologues of the vertebrate cannabinoid receptors are not found in protostomian invertebrates (e.g. Drosophila, Caenorhabditis elegans). Therefore, it is likely that a CB1/CB2-type cannabinoid receptor originated in a deuterostomian invertebrate. This phylogenetic information provides a basis for exploitation of selected non-mammalian organisms as model systems for research on endocannabinoid signalling.

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References

  • Adams MD, Celniker SE, Holt RA, et al (2000) The genome sequence of Drosophila melanogaster. Science 287:2185–2195

    Article  PubMed  Google Scholar 

  • Adoutte A, Balavoine G, Lartillot N, Lespinet O, Prud’homme B, De Rosa R (2000) The new animal phylogeny: reliability and implications. Proc Natl Acad Sci USA 97:4453–4456

    Article  PubMed  CAS  Google Scholar 

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410

    Article  PubMed  CAS  Google Scholar 

  • Aparicio S, Chapman J, Stupka E, et al (2002) Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes. Science 297:1301–1310

    Article  PubMed  CAS  Google Scholar 

  • Bisogno T, Ventriglia M, Milone A, Mosca M, Cimino G, Di Marzo V (1997) Occurrence and metabolism of anandamide and related acyl-ethanolamides in ovaries of the sea urchin Paracentrotus lividus. Biochim Biophys Acta 1345:338–348

    PubMed  Google Scholar 

  • Bisogno T, Howell F, Williams G, Minassiz A, Cascio MG, Ligresti A, Matias I, Schiano-Moriello A, Paul P, Williams EJ, Gangadharan U, Hobbs C, Di Marzo V, Doherty P (2003) Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain. J Cell Biol 163:463–468

    Article  PubMed  CAS  Google Scholar 

  • Breivogel CS, Griffin G, Di Marzo V, Martin BR (2001) Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. Mol Pharmacol 60:155–163

    PubMed  CAS  Google Scholar 

  • Cameron RA, Mahairas G, Rast JP, Martinez P, Biondi TR, Swartzell S, Wallace JC, Poustka AJ, Livingston BT, Wray GA, Ettensohn CA, Lehrach H, Britten RJ, Davidson EH, Hood L (2000) A sea urchin genome project: sequence scan, virtual map, and additional resources. Proc Natl Acad Sci USA 97:9514–9518

    PubMed  Google Scholar 

  • Chang MC, Berkery D, Schuel R, Laychock SG, Zimmerman AM, Zimmerman S, Schuel H (1993) Evidence for a cannabinoid receptor in sea urchin spermand its role in blockade of the acrosome reaction. Mol Reprod Dev 36:507–516

    Article  PubMed  CAS  Google Scholar 

  • Chapman KD (2000) Emerging physiological roles for N-acylphosphatidylethanolamine metabolism in plants: signal transduction and membrane protection. Chem Phys Lipids 108:221–229

    Article  PubMed  CAS  Google Scholar 

  • Cravatt BF, Giang DK, Mayfield SP, Boger DL, Lerner RA, Guilula NB (1996) Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 384:83–87

    Article  PubMed  CAS  Google Scholar 

  • De Petrocellis L, Melck D, Bisogno T, Milone A, Di Marzo V (1999) Finding of the endocannabinoid signalling system in Hydra, a very primitive organism: possible role in the feeding response. Neuroscience 92:377–387

    PubMed  Google Scholar 

  • Dehal P, Satou Y, Campbell RK, et al (2002) The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins. Science 298:2157–2167

    Article  PubMed  CAS  Google Scholar 

  • Deutsch DG, Chin SA (1993) Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist. Biochem Pharmacol 46:791–796

    Article  PubMed  CAS  Google Scholar 

  • Devane WA, Dysarz FAI, Johnson MR, Melvin LS, Howlett AC (1988) Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 34:605–613

    PubMed  CAS  Google Scholar 

  • Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946–1948

    PubMed  CAS  Google Scholar 

  • Di Marzo V, Fontana A, Cadas H, Schinelli S, Cimino G, Schwartz J-C, Piomelli D (1994) Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 372:686–691

    PubMed  Google Scholar 

  • Dinh TP, Carpenter D, Leslie FM, Freund TF, Katona I, Sensi L, Kathuria S, Piomelli D (2002) Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci USA 99:10819–10824

    Article  PubMed  CAS  Google Scholar 

  • Egertová M (1999) Neuroanatomy and phylogeny of cannabinoid signalling. Ph.D. Thesis, University of London, UK

    Google Scholar 

  • Egertová M, Giang DK, Cravatt BF, Elphick MR (1998) A new perspective on cannabinoid signalling: complementary localization of fatty acid amide hydrolase and the CB1 receptor in rat brain. Proc R Soc Lond B Biol Sci 265:2081–2085

    Article  Google Scholar 

  • Elphick MR (1998) An invertebrate G-protein coupled receptor is a chimeric cannabinoid/melanocortin receptor. Brain Res 780:170–173

    Article  PubMed  CAS  Google Scholar 

  • Elphick MR (2002) Evolution of cannabinoid receptors in vertebrates: identification of a CB2 gene in the puffer fish Fugu rubripes. Biol Bull 202:104–107

    PubMed  CAS  Google Scholar 

  • Elphick MR, Egertová M (2001) The neurobiology and evolution of cannabinoid signalling. Philos Trans R Soc Lond B Biol Sci 356:381–408

    PubMed  CAS  Google Scholar 

  • Elphick MR, Satou Y, Satoh N (2003) The invertebrate ancestry of endocannabinoid signalling: an orthologue of vertebrate cannabinoid receptors in the urochordate Ciona intestinalis. Gene 302:95–101

    Article  PubMed  CAS  Google Scholar 

  • Freund TF, Katona I, Piomelli D (2003) Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 83:1017–1066

    PubMed  CAS  Google Scholar 

  • Furlong RF, Holland PWH (2002) Were vertebrates octoploid? Philos Trans R Soc Lond B Biol Sci 357:531–544

    PubMed  CAS  Google Scholar 

  • Giang DK, Cravatt BF (1997) Molecular characterization of human and mouse fatty acid amide hydrolases. Proc Natl Acad Sci USA 94:2238–2242

    Article  PubMed  CAS  Google Scholar 

  • Goparaju SK, Ueda N, Yamaguchi H, Yamamoto S (1998) Anandamide amidohydrolase reacting with 2-arachidonoylglycerol, another cannabinoid receptor ligand. FEBS Lett 422:69–73

    Article  PubMed  CAS  Google Scholar 

  • Hastings N, Agaba M, Tocher DR, Leaver MJ, Dick JR, Sargent JR, Teale AJ (2001) A vertebrate fatty acid desaturase with delta 5 and delta 6 activities. Proc Natl Acad Sci USA 98:14304–14309

    Article  PubMed  CAS  Google Scholar 

  • Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, Felder CC, Herkenham M, Mackie K, Martin BR, Mechoulam R, Pertwee RG (2002) International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 54:161–202

    Article  PubMed  CAS  Google Scholar 

  • Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Hogestatt ED, Meng ID, Julius D (2004) Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427:260–265

    Article  PubMed  CAS  Google Scholar 

  • Karlsson M, Contreras JA, Hellman U, Tornqvist H, Holm C (1997) cDNA cloning, tissue distribution, and identification of the catalytic triad of monoglyceride lipase. Evolutionary relationship to esterases, lysophospholipases, and haloperoxidases. J Biol Chem 27:27218–27223

    Google Scholar 

  • Kreitzer AC, Regehr WG (2002) Retrograde signaling by endocannabinoids. Curr Opin Neurobiol 12:324–330

    Article  PubMed  CAS  Google Scholar 

  • Lichtman AH, Hawkins EG, Griffin G, Cravatt BF (2002) Pharmacological activity of fatty acid amides is regulated, but not mediated, by fatty acid amide hydrolase in vivo. J Pharmacol Exp Ther 302:73–79

    Article  PubMed  CAS  Google Scholar 

  • Lowe CJ, Wu M, Salic A, Evans L, Lander E, Stange-Thomann N, Gruber CE, Gerhart J, Kirschner M (2003) Anteroposterior patterning in hemichordates and the origins of the chordate nervous system. Cell 113:853–865

    Article  PubMed  CAS  Google Scholar 

  • Matias I, Bisogno T, Melck D, Vandenbulcke F, Verger-Bocquet M, De Petrocellis L, Sergheraert C, Breton C, Di Marzo V, Salzet M (2001) Evidence for an endocannabinoid system in the central nervous system of the leech Hirudo medicinalis. Brain Res Mol Brain Res 87:145–159

    PubMed  CAS  Google Scholar 

  • Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564

    Article  PubMed  CAS  Google Scholar 

  • McPartland JM, Pruitt P (2002) Sourcing the code: searching for the evolutionary origins of cannabinoid receptors, vanilloid receptors, and anandamide. J Cannabis Ther 2:73–103

    CAS  Google Scholar 

  • McPartland J, Di Marzo V, De Petrocellis L, Mercer A, Glass M (2001) Cannabinoid receptor are absent in insects. J Comp Neurol 436:423–429

    Article  PubMed  CAS  Google Scholar 

  • Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR, Pertwee RG, Griffin G, Bayewitch M, Barg J, Vogel ZVI (1995) Identification of an endogenous 2-monoglyceride, present in canine gut that binds to cannabinoid receptors. Biochem Pharmacol 50:83–90

    Article  PubMed  CAS  Google Scholar 

  • Montell C (2003) The venerable inveterate invertebrate TRP channels. Cell Calcium 33:409–417

    Article  PubMed  CAS  Google Scholar 

  • Montell C, Birnbaumer L, Flockerzi V (2002) The TRP channels, a remarkably functional family. Cell 108:595–598

    Article  PubMed  CAS  Google Scholar 

  • Munro S, Thomas KL, Abu-Shaar M (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61–65

    Article  PubMed  CAS  Google Scholar 

  • Nakamura MT, Nara TY (2003) Essential fatty acid synthesis and its regulation in mammals. Prostaglandins Leukot Essent Fatty Acids 68:145–150

    Article  PubMed  CAS  Google Scholar 

  • Napier J, Michaelson LV (2001) Genomic and functional characterisation of polyunsaturated fatty acid biosynthesis in Caenorhabditis elegans. Lipids 36:761–766

    PubMed  CAS  Google Scholar 

  • Okamoto Y, Morishita J, Tsuboi K, Tonai T, Ueda N (2004) Molecular characterization of a phospholipase D generating anandamide and its congeners. J Biol Chem 279:5298–5305

    Article  PubMed  CAS  Google Scholar 

  • Piomelli D (2003) The molecular logic of endocannabinoid signalling. Nat Rev Neurosci 4:873–884

    Article  PubMed  CAS  Google Scholar 

  • Salzet M, Stefano G (2002) The endocannabinoid system in invertebrates. Prostaglandins Leukot Essent Fatty Acids 66:353–361

    Article  PubMed  CAS  Google Scholar 

  • Salzet M, Breton C, Bisogno T, Di Marzo V (2000) Comparative biology of the endocannabinoid system. Possible role in the immune response. Eur J Biochem 15:4917–4927

    Google Scholar 

  • Schmid HH, Schmid PC, Natarajan V (1990) N-Acylated glycerophospholipids and their derivatives. Prog Lipid Res 29:1–43

    Article  PubMed  CAS  Google Scholar 

  • Schuel H, Berkery D, Schuel R, Chang MC, Zimmerman AM, Zimmerman S (1991) Reduction of the fertilizing capacity of sea urchin spermby cannabinoids derived from marihuana. I. Inhibition of the acrosome reaction induced by egg jelly. Mol Reprod Dev 29:51–59

    Article  PubMed  CAS  Google Scholar 

  • Schuel H, Goldstein E, Mechoulam R, Zimmerman AM, Zimmerman S (1994) Anandamide (arachidonylethanolamide), a brain cannabinoid receptor agonist, reduces sperm fertilizing capacity in sea urchins by inhibiting the acrosome reaction. Proc Natl Acad Sci USA 91:7678–7682

    PubMed  CAS  Google Scholar 

  • Shrestha R, Noordermeer MA, van der Stelt M, Veldink GA, Chapman KD (2002) NAcylethanolamines are metabolised by lipoxygenase and amidohydrolase in competing pathways during cottonseed imbibition. Plant Physiol 130:391–401

    Article  PubMed  CAS  Google Scholar 

  • Shrestha R, Dixon RA, Chapman KD (2003) Molecular identification of a functional homologue of the mammalian fatty acid amide hydrolase in Arabidopsis thaliana. J Biol Chem 278:34990–34997

    Article  PubMed  CAS  Google Scholar 

  • Soderstrom K, Johnson F (2000) CB1 cannabinoid receptor expression in brain regions associated with zebra finch song control. Brain Res 857:151–157

    Article  PubMed  CAS  Google Scholar 

  • Soderstrom K, Johnson F (2001) Zebra finch CB1 cannabinoid receptor: pharmacology and in vivo and in vitro effects of activation. J Pharmacol Exp Ther 297:189–197

    PubMed  CAS  Google Scholar 

  • Soderstrom K, Leid M, Moore FL, Murray TF (2000) Behavioural, pharmacological and molecular characterization of an amphibian cannabinoid receptor. J Neurochem 75:413–423

    Article  PubMed  CAS  Google Scholar 

  • Stefano GB, Liu Y, Goligorsky MS (1996) Cannabinoid receptors are coupled to nitric oxide release in invertebrate immunocytes, microglia and human monocytes. J Biol Chem 271:19238–19242

    PubMed  CAS  Google Scholar 

  • Stefano GB, Salzet B, Salzet M (1997) Identification and characterization of the leech CNS cannabinoid receptor: coupling to nitric oxide release. Brain Res 753:219–224

    Article  PubMed  CAS  Google Scholar 

  • Sugiura T, Kondo S, Sukagawa A, Nakane S, Shinoda A, Itoh K, Yamashita A, Waku K (1995) 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun 215:89–97

    Article  PubMed  CAS  Google Scholar 

  • Taylor JS, Van de Peer Y, Braasch I, Meyer A (2001) Comparative genomics provides evidence for an ancient genome duplication event in fish. Philos Trans R Soc Lond B Biol Sci 356:1661–1679

    PubMed  CAS  Google Scholar 

  • TheC. elegans Sequencing Consortium (1998) Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282:2012–2018

    Google Scholar 

  • Tripathy S, Kleppinger-Sparace K, Dixon RA, Chapman KD (2003) N-acylethanolamine signaling in tobacco is mediated by a membrane-associated, high-affinity binding protein. Plant Physiol 131:1781–1791

    Article  PubMed  CAS  Google Scholar 

  • Ueda N, Kurahashi Y, Yamamoto S, Tokunaga T (1995) Partial purification and characterization of the porcine brain enzyme hydrolyzing and synthesizing anandamide. J Biol Chem 270:23823–23827

    PubMed  CAS  Google Scholar 

  • Wilson RI, Nicoll RA (2002) Endocannabinoid signaling in the brain. Science 296:678–682

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi F, Macrae AD, Brenner S (1996) Molecular cloning of two cannabinoid type 1-like receptor genes from the puffer fish Fugu rubripes. Genomics 35:603–605

    Article  PubMed  CAS  Google Scholar 

  • Yoshioka T, Inoue H, Kasama T, Seyama Y, Nakashima S, Nozawa Y, Hotta Y (1985) Evidence that arachidonic acid is deficient in phosphatidylinositol of Drosophila heads. J Biochem (Tokyo) 98:657–662

    PubMed  CAS  Google Scholar 

  • Zygmunt PM, Petersson J, Andersson DA, Chuang HH, Sorgard M, Di Marzo V, Julius D, Hogestatt ED (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400:452–457

    PubMed  CAS  Google Scholar 

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  1. M. R. Elphick

    Present address: School of Biological Sciences, Queen Mary, University of London, London, E1 4NS, UK

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  1. School of Biological Sciences, Queen Mary, University of London, London, E1 4NS, UK

    M. Egertová

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  1. M. R. Elphick
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  1. School of Medical Sciences, Institute of Medical Science, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, Scotland, UK

    Roger G. Pertwee

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Elphick, M.R., Egertová, M. (2005). The Phylogenetic Distribution and Evolutionary Origins of Endocannabinoid Signalling. In: Pertwee, R.G. (eds) Cannabinoids. Handbook of Experimental Pharmacology, vol 168. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-26573-2_9

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