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The Endocannabinoid System and its Modulation by Phytocannabinoids

The Endocannabinoid System and its Modulation by Phytocannabinoids The endocannabinoid system is currently defined as the ensemble of the two 7-transmembrane-domain and G protein-coupled receptors for Δ9-tetrahydrocannabinol (but not for most other plant cannabinoids or phytocannabinoids)—cannabinoid receptor type-1 (CB1R) and cannabinoid receptor type-2 (CB2R); their two most studied endogenous ligands, the “endocannabinoids” N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG); and the enzymes responsible for endocannabinoid metabolism. However, anandamide and 2-AG, and also the phytocannabinoids, have more molecular targets than just CB1R and CB2R. Furthermore, the endocannabinoids, like most other lipid mediators, have more than just one set of biosynthetic and degrading pathways and enzymes, which they often share with “endocannabinoid-like” mediators that may or may not interact with the same proteins as Δ9-tetrahydrocannabinol and other phytocannabinoids. In some cases, these degrading pathways and enzymes lead to molecules that are not inactive and instead interact with other receptors. Finally, some of the metabolic enzymes may also participate in the chemical modification of molecules that have very little to do with endocannabinoid and cannabinoid targets. Here, we review the whole world of ligands, receptors, and enzymes, a true “endocannabinoidome”, discovered after the cloning of CB1R and CB2R and the identification of anandamide and 2-AG, and its interactions with phytocannabinoids. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurotherapeutics Springer Journals

The Endocannabinoid System and its Modulation by Phytocannabinoids

Di Marzo, Vincenzo; Piscitelli, Fabiana
Neurotherapeutics , Volume 12 (4) – Aug 14, 2015
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Publisher
Springer Journals
Copyright
Copyright © 2015 by The American Society for Experimental NeuroTherapeutics, Inc.
Subject
Biomedicine; Neurosciences; Neurology; Neurosurgery; Neurobiology
ISSN
1933-7213
eISSN
1878-7479
DOI
10.1007/s13311-015-0374-6
pmid
26271952
Publisher site
See Article on Publisher Site

Abstract

The endocannabinoid system is currently defined as the ensemble of the two 7-transmembrane-domain and G protein-coupled receptors for Δ9-tetrahydrocannabinol (but not for most other plant cannabinoids or phytocannabinoids)—cannabinoid receptor type-1 (CB1R) and cannabinoid receptor type-2 (CB2R); their two most studied endogenous ligands, the “endocannabinoids” N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG); and the enzymes responsible for endocannabinoid metabolism. However, anandamide and 2-AG, and also the phytocannabinoids, have more molecular targets than just CB1R and CB2R. Furthermore, the endocannabinoids, like most other lipid mediators, have more than just one set of biosynthetic and degrading pathways and enzymes, which they often share with “endocannabinoid-like” mediators that may or may not interact with the same proteins as Δ9-tetrahydrocannabinol and other phytocannabinoids. In some cases, these degrading pathways and enzymes lead to molecules that are not inactive and instead interact with other receptors. Finally, some of the metabolic enzymes may also participate in the chemical modification of molecules that have very little to do with endocannabinoid and cannabinoid targets. Here, we review the whole world of ligands, receptors, and enzymes, a true “endocannabinoidome”, discovered after the cloning of CB1R and CB2R and the identification of anandamide and 2-AG, and its interactions with phytocannabinoids.

Journal

Neurotherapeutics – Springer Journals

Published: Aug 14, 2015

References

  • The endocannabinoid system: directing eating behavior and macronutrient metabolism
    Watkins, BA; Kim, J
  • Non-CB1, non-CB2 receptors for endocannabinoids, plant cannabinoids, and synthetic cannabimimetics: focus on G-protein-coupled receptors and transient receptor potential channels
    Petrocellis, L; Marzo, V
  • Overlap between the ligand recognition properties of the anandamide transporter and the VR1 vanilloid receptor: inhibitors of anandamide uptake with negligible capsaicin-like activity
    Petrocellis, L; Bisogno, T; Davis, JB; Pertwee, RG; Marzo, V
  • Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide
    Zygmunt, PM; Petersson, J; Andersson, DA
  • Activation of TRPV1 by the satiety factor oleoylethanolamide
    Ahern, GP
  • Regulation of transient receptor potential channels of melastatin type 8 (TRPM8): effect of cAMP, cannabinoid CB(1) receptors and endovanilloids
    Petrocellis, L; Starowicz, K; Moriello, AS; Vivese, M; Orlando, P; Marzo, V
  • Why do cannabinoid receptors have more than one endogenous ligand?
    Marzo, V; Petrocellis, L
  • Monoacylglycerols activate TRPV1—a link between phospholipase C and TRPV1
    Zygmunt, PM; Ermund, A; Movahed, P
  • Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8
    Petrocellis, L; Vellani, V; Schiano-Moriello, A
  • Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes
    Petrocellis, L; Ligresti, A; Moriello, AS
  • Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation
    Petrocellis, L; Orlando, P; Moriello, AS
  • Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability
    Iannotti, FA; Hill, CL; Leo, A
  • TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons
    Qin, N; Neeper, MP; Liu, Y; Hutchinson, TL; Lubin, ML; Flores, CM
  • Role of ionotropic cannabinoid receptors in peripheral antinociception and antihyperalgesia
    Akopian, AN; Ruparel, NB; Jeske, NA; Patwardhan, A; Hargreaves, KM
  • Endocannabinoids as regulators of transient receptor potential (TRP) channels: a further opportunity to develop new endocannabinoid-based therapeutic drugs
    Marzo, V; Petrocellis, L
  • Palmitoylethanolamide enhances anandamide stimulation of human vanilloid VR1 receptors
    Petrocellis, L; Davis, JB; Marzo, V
  • Activation and desensitization of TRPV1 channels in sensory neurons by the PPARα agonist palmitoylethanolamide
    Ambrosino, P; Soldovieri, MV; Russo, C; Taglialatela, M
  • An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors
    Huang, SM; Bisogno, T; Trevisani, M
  • Endogenous unsaturated C18 N-acylethanolamines are vanilloid receptor (TRPV1) agonists
    Movahed, P; Jönsson, BA; Birnir, B
  • New N-arachidonoylserotonin analogues with potential “dual” mechanism of action against pain
    Ortar, G; Cascio, MG; Petrocellis, L
  • Presence, formation and putative biological activities of N-acyl serotonins, a novel class of fatty-acid derived mediators, in the intestinal tract
    Verhoeckx, KC; Voortman, T; Balvers, MG; Hendriks, HF; Wortelboer, MH; Witkamp, RF
  • Evidence that the plant cannabinoid Delta9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist
    Thomas, A; Stevenson, LA; Wease, KN
  • Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide
    Bisogno, T; Hanus, L; Petrocellis, L
  • Effect of cannabidiol on sepsis-induced motility disturbances in mice: involvement of CB receptors and fatty acid amide hydrolase
    Filippis, D; Iuvone, T; d'amico, A
  • Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia
    Leweke, FM; Piomelli, D; Pahlisch, F
  • Are cannabidiol and Δ(9)-tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review
    McPartland, JM; Duncan, M; Marzo, V; Pertwee, RG
  • The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin
    Pertwee, RG
  • The plant cannabinoid Delta9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice
    Bolognini, D; Costa, B; Maione, S
  • Mead ethanolamide, a novel eicosanoid, is an agonist for the central (CB1) and peripheral (CB2) cannabinoid receptors
    Priller, J; Briley, EM; Mansouri, J; Devane, WA; Mackie, K; Felder, CC
  • Cannabinoid receptor-dependent and -independent anti-proliferative effects of omega-3 ethanolamides in androgen receptor-positive and -negative prostate cancer cell lines
    Brown, I; Cascio, MG; Wahle, KW
  • Oleamide is a selective endogenous agonist of rat and human CB1 cannabinoid receptors
    Leggett, JD; Aspley, S; Beckett, SR; D'Antona, AM; Kendall, DA; Kendall, DA
  • Biosynthesis, uptake, and degradation of anandamide and palmitoylethanolamide in leukocytes
    Bisogno, T; Maurelli, S; Melck, D; Petrocellis, L; Marzo, V
  • Regulation of anandamide tissue levels by N-arachidonylglycine
    Burstein, SH; Huang, SM; Petros, TJ; Rossetti, RG; Walker, JM; Zurier, RB
  • The endocannabinoid anandamide is a precursor for the signaling lipid N-arachidonoyl glycine by two distinct pathways
    Bradshaw, HB; Rimmerman, N; Hu, SS
  • A FAAH-regulated class of N-acyl taurines that activates TRP ion channels
    Saghatelian, A; McKinney, MK; Bandell, M; Patapoutian, A; Cravatt, BF
  • Palmitoylethanolamide inhibits the expression of fatty acid amide hydrolase and enhances the anti-proliferative effect of anandamide in human breast cancer cells
    Marzo, V; Melck, D; Orlando, P
  • An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity
    Ben-Shabat, S; Fride, E; Sheskin, T
  • The orphan receptor GPR55 is a novel cannabinoid receptor
    Ryberg, E; Larsson, N; Sjögren, S
  • CB1 and GPR55 receptors are co-expressed and form heteromers in rat and monkey striatum
    Martínez-Pinilla, E; Reyes-Resina, I; Oñatibia-Astibia, A
  • The endocannabinoids anandamide and virodhamine modulate the activity of the candidate cannabinoid receptor GPR55
    Sharir, H; Console-Bram, L; Mundy, C; Popoff, SN; Kapur, A; Abood, ME
  • Atypical responsiveness of the orphan receptor GPR55 to cannabinoid ligands
    Kapur, A; Zhao, P; Sharir, H
  • GPR55 and GPR35 and their relationship to cannabinoid and lysophospholipid receptors
    Zhao, P; Abood, ME
  • Identification of N-arachidonylglycine as the endogenous ligand for orphan G-protein-coupled receptor GPR18
    Kohno, M; Hasegawa, H; Inoue, A
  • Activation of GPR18 by cannabinoid compounds: a tale of biased agonism
    Console-Bram, L; Brailoiu, E; Brailoiu, GC; Sharir, H; Abood, ME
  • Cross-modulation and molecular interaction at the Cav3.3 protein between the endogenous lipids and the T-type calcium channel antagonist TTA-A2
    Cazade, M; Nuss, CE; Bidaud, I
  • Inhibition of recombinant human T-type calcium channels by Delta9-tetrahydrocannabinol and cannabidiol
    Ross, HR; Napier, I; Connor, M
  • The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide
    Lo Verme, J; Fu, J; Astarita, G
  • Cannabinoid activation of PPAR alpha; a novel neuroprotective mechanism
    Sun, Y; Alexander, SP; Garle, MJ
  • Cannabidiol promotes amyloid precursor protein ubiquitination and reduction of beta amyloid expression in SHSY5YAPP+ cells through PPARγ involvement
    Scuderi, C; Steardo, L; Esposito, G
  • Cannabinoids go nuclear: evidence for activation of peroxisome proliferator-activated receptors
    O'Sullivan, SE
  • Endocannabinoids anandamide and 2-arachidonoylglycerol are substrates for human CYP2J2 epoxygenase
    McDougle, DR; Kambalyal, A; Meling, DD; Das, A
  • Characterization of cannabidiol-mediated cytochrome P450 inactivation
    Bornheim, LM; Everhart, ET; Li, J; Correia, MA
  • Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis
    Takeda, S; Misawa, K; Yamamoto, I; Watanabe, K