The molecular machinery required to process endocannabinoids lipid signaling and their respective receptors
A maquinaria molecular necessária para processar mensageiros lipídicos endocanabinoides e seus respectivos receptores
Tiago Marques Avelar; Leonardo Rafael Takahashi; José Oswaldo de Oliveira Junior
Abstract
BACKGROUND AND OBJECTIVES: Pharmaceutical preparations of cannabis have been used by mankind since long time ago, and recently they have been the pharmaceutical industry’s focus. However, for proper therapeutic application, in-depth knowledge of the endocannabinoid system, which is made mainly by lipid signaling, is needed. The purpose of this study was to explore the current understanding of the players in this system, paying special attention to the molecular machinery required to process it.
CONTENTS: This is a narrative review of the current literature regarding major components of the endocannabinoid system, in particular: the receptors, main endogenous ligands, and the enzymes responsible for its components processing. The pharmacological and preclinical aspects were emphasized.
CONCLUSION: The better comprehension of the molecular structure of receptors and enzymes will be crucial to developing new pharmacological strategies. A detailed description of the machinery responsible for endocannabinoid lipid metabolization will pave the way for the discovery of new drugs that act on the endogenous system and that can be applied effectively in clinical practice.
Keywords
Resumo
JUSTIFICATIVA E OBJETIVOS: Os preparados medicinais canabinoides são há muito utilizados pela humanidade e têm sido objeto de interesse da indústria farmacológica recente. Para a aplicação terapêutica adequada é necessário, no entanto, o conhecimento aprofundado do sistema canabinoide endógeno, o qual em sua grande parte é constituído por mensageiros lipídicos. O objetivo deste estudo foi explorar o conhecimento vigente a respeito dos constituintes desse sistema, com especial atenção à maquinaria molecular necessária para processá-los.
CONTEÚDO: Trata-se de uma revisão narrativa da literatura atual acerca dos integrantes do sistema canabinoide endógeno, notadamente: seus receptores, os principais ligantes endógenos e as enzimas responsáveis pelo processamento de seus componentes. Os aspectos farmacológicos e pré-clínicos foram enfatizados.
CONCLUSÃO: O melhor entendimento da ultraestrutura de receptores e enzimas contribuirá de forma decisiva para o desenvolvimento de novas estratégias farmacológicas. A partir da descrição pormenorizada da maquinaria responsável pela metabolização lipídica endocanabinoide é que se pavimentará o caminho para a descoberta de novos fármacos que atuem no sistema endógeno e que possam ser aplicados de forma eficaz na prática clínica.
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References
1 Mechoulam R. The Pharmacohistory of Cannabis Sativa. In: Cannabinoids as Therapeutic Agents. Chapman and Hall/CRC; 1986.
2 Pertwee RG. Cannabinoid pharmacology: the first 66 years. Br J Pharmacol. 2006;147(Suppl 1):S163-71.
3 Mechoulam R, Gaoni Y. The absolute configuration of delta-1-tetrahydrocannabinol, the major active constituent of hashish. Tetrahedron Lett. 1967;12:1109-11.
4 Devane WA, Dysarz FA, Johnson MR, Melvin LS, Howlett AC. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol. 1988;34(5):605-13.
5 Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature. 1993;365(6441):61-5.
6 Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992 Dec 18;258(5090):1946-9.
7 Sugiura T, Kondo S, Sukagawa A, Nakane S, Shinoda A, Itoh K, Yamashita A, Waku K. 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun. 1995;215(1):89-97.
8 Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol. 1995;50(1):83-90.
9 Zou S, Kumar U. Cannabinoid receptors and the endocannabinoid system: signaling and function in the central nervous system. Int J Mol Sci. 2018;19(3):833.
10 Di Marzo V, De Petrocellis L. Why do cannabinoid receptors have more than one endogenous ligand? Philos Trans R Soc Lond B Biol Sci. 2012;367(1607):3216-28.
11 Woodhams SG, Sagar DR, Burston JJ, Chapman V. The role of the endocannabinoid system in pain. Handb Exp Pharmacol. 2015;227:119-43.
12 Shahbazi F, Grandi V, Banerjee A, Trant JF. Cannabinoids and cannabinoid receptors: the story so far. iScience. 2020;23(7):101301.
13 Hauser AS, Attwood MM, Rask-Andersen M, Schiöth HB, Gloriam DE. Trends in GPCR drug discovery: new agents, targets and indications. Nat Rev Drug Discov. 2017;16(12):829-42.
14 Weis WI, Kobilka BK. The molecular basis of G protein-coupled receptor activation. Annu Rev Biochem. 2018;87(1):897-919.
15 Latorraca NR, Venkatakrishnan AJ, Dror RO. GPCR dynamics: structures in motion. Chem Rev. 2017;117(1):139-55.
16 Bond RA, Leff P, Johnson TD, Milano CA, Rockman HA, McMinn TR, Apparsundaram S, Hyek MF, Kenakin TP, Allen LF, et al. Physiological effects of inverse agonists in transgenic mice with myocardial overexpression of the beta 2-adrenoceptor. Nature. 1995;374(6519):272-6.
17 Vilardaga J-P, Steinmeyer R, Harms GS, Lohse MJ. Molecular basis of inverse agonism in a G protein-coupled receptor. Nat Chem Biol. 2005;1(1):25-8.
18 Yu Y, Li L, Nguyen DT, Mustafa SM, Moore BM, Jiang J. Inverse agonism of cannabinoid receptor type 2 confers anti-inflammatory and neuroprotective effects following status epileptics. Mol Neurobiol. 2020;57(6):2830-45.
19 Mewes T, Dutz S, Ravens U, Jakobs KH. Activation of calcium currents in cardiac myocytes by empty beta-adrenoceptors. Circulation. 1993;88(6):2916-22.
20 Kuznetsov AS, Zamaletdinov MF, Bershatsky YV, Urban AS, Bocharova OV, Bennasroune A, et al. Dimeric states of transmembrane domains of insulin and IGF-1R receptors: structures and possible role in activation. Biochim Biophys Acta Biomembr. 2020;1862(11):183417.
21 Mafi A, Kim S-K, Iii WAG. The G protein-first activation mechanism of opioid receptors by Gi protein and agonists. QRB Discov 2 E9. 2021;14.
22 Nakanishi J, Takarada T, Yunoki S, Kikuchi Y, Maeda M. FRET-based monitoring of conformational change of the β2 adrenergic receptor in living cells. Biochem Biophys Res Commun. 2006;343(4):1191-6.
23 Jensen AD, Guarnieri F, Rasmussen Søren GF, Asmar F, Ballesteros JA, Gether U. Agonist-induced conformational changes at the cytoplasmic side of transmembrane segment 6 in the β2 adrenergic receptor mapped by site-selective fluorescent labeling*. J Biol Chem. 2001;276(12):9279-90.
24 Xing C, Zhuang Y, Xu TH, Feng Z, Zhou XE, Chen M, Wang L, Meng X, Xue Y, Wang J, Liu H, McGuire TF, Zhao G, Melcher K, Zhang C, Xu HE, Xie XQ. Cryo-EM structure of the human cannabinoid receptor CB2-Gi signaling complex. Cell. 2020 Feb 20;180(4):645-54.e13.
25 Hua T, Li X, Wu L, Iliopoulos-Tsoutsouvas C, Wang Y, Wu M, Shen L, Brust CA, Nikas SP, Song F, Song X, Yuan S, Sun Q, Wu Y, Jiang S, Grim TW, Benchama O, Stahl EL, Zvonok N, Zhao S, Bohn LM, Makriyannis A, Liu ZJ. Activation and signaling mechanism revealed by cannabinoid receptor-Gi complex structures. Cell. 2020;180(4):655-65.e18.
26 Li X, Hua T, Vemuri K, Ho JH, Wu Y, Wu L, Popov P, Benchama O, Zvonok N, Locke K, Qu L, Han GW, Iyer MR, Cinar R, Coffey NJ, Wang J, Wu M, Katritch V, Zhao S, Kunos G, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ. Crystal structure of the human cannabinoid receptor CB2. Cell. 2019;176(3):459-67.e13.
27 Krishna Kumar K, Shalev-Benami M, Robertson MJ, Hu H, Banister SD, Hollingsworth SA, Latorraca NR, Kato HE, Hilger D, Maeda S, Weis WI, Farrens DL, Dror RO, Malhotra SV, Kobilka BK, Skiniotis G. Structure of a signaling cannabinoid receptor 1-G protein complex. Cell. 2019;176(3):448-58.e12.
28 Hua T, Vemuri K, Nikas SP, Laprairie RB, Wu Y, Qu L, Pu M, Korde A, Jiang S, Ho JH, Han GW, Ding K, Li X, Liu H, Hanson MA, Zhao S, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ. Crystal structures of agonist-bound human cannabinoid receptor CB 1. Nature. 2017;547(7664):468-71.
29 Shao Z, Yin J, Chapman K, Grzemska M, Clark L, Wang J, Rosenbaum DM. High-resolution crystal structure of the human CB1 cannabinoid receptor. Nature. 2016;540(7634):602-6.
30 Hryhorowicz S, Kaczmarek-Ryś M, Andrzejewska A, Staszak K, Hryhorowicz M, Korcz A, Słomski R. Allosteric modulation of cannabinoid receptor 1-current challenges and future opportunities. Int J Mol Sci. 2019;20(23):5874.
31 Patricia HR. Endocannabinoid binding to the cannabinoid receptors: what is known and what remains unknown. Curr Med Chem. 2010;17(14):1468-86.
32 Montero C, Campillo NE, Goya P, Páez JA. Homology models of the cannabinoid CB1 and CB2 receptors. A docking analysis study. Eur J Med Chem. 2005;40(1):75-83.
33 Amin MR, Ali DW. Pharmacology of medical cannabis. Adv Exp Med Biol. 2019;1162:151-65.
34 Baker D, Pryce G, Giovannoni G, Thompson AJ. The therapeutic potential of cannabis. Lancet Neurol. 2003;2(5):291-8.
35 Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, Felder CC, Herkenham M, Mackie K, Martin BR, Mechoulam R, Pertwee RG. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev. 2002;54(2):161-202.
36 Tam J, Trembovler V, Di Marzo V, Petrosino S, Leo G, Alexandrovich A, Regev E, Casap N, Shteyer A, Ledent C, Karsak M, Zimmer A, Mechoulam R, Yirmiya R, Shohami E, Bab I. The cannabinoid CB1 receptor regulates bone formation by modulating adrenergic signaling. FASEB J. 2008;22(1):285-94.
37 Veress G, Meszar Z, Muszil D, Avelino A, Matesz K, Mackie K, Nagy I. Characterisation of cannabinoid 1 receptor expression in the perikarya, and peripheral and spinal processes of primary sensory neurons. Brain Struct Funct. 2013;218(3):733-50.
38 Clapper JR, Moreno-Sanz G, Russo R, Guijarro A, Vacondio F, Duranti A, Tontini A, Sanchini S, Sciolino NR, Spradley JM, Hohmann AG, Calignano A, Mor M, Tarzia G, Piomelli D. Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism. Nat Neurosci. 2010;13(10):1265-70.
39 Price TJ, Helesic G, Parghi D, Hargreaves KM, Flores CM. The neuronal distribution of cannabinoid receptor type 1 in the trigeminal ganglion of the rat. Neuroscience. 2003;120(1):155-62.
40 Mackie K. Cannabinoid receptors: where they are and what they do. J Neuroendocrinol. 2008;20(s1):10-4.
41 Brailoiu GC, Deliu E, Marcu J, Hoffman NE, Console-Bram L, Zhao P, Madesh M, Abood ME, Brailoiu E. Differential activation of intracellular versus plasmalemmal CB2 cannabinoid receptors. Biochemistry. 2014;53(30):4990-9.
42 den Boon FS, Chameau P, Schaafsma-Zhao Q, van Aken W, Bari M, Oddi S, Kruse CG, Maccarrone M, Wadman WJ, Werkman TR. Excitability of prefrontal cortical pyramidal neurons is modulated by activation of intracellular type-2 cannabinoid receptors. Proc Natl Acad Sci U S A. 2012;109(9):3534-9.
43 Dhopeshwarkar A, Mackie K. CB2 Cannabinoid receptors as a therapeutic target-what does the future hold? Mol Pharmacol. 2014;86(4):430-7.
44 Atwood BK, Mackie K. CB2: a cannabinoid receptor with an identity crisis. Br J Pharmacol. 2010;160(3):467-79.
45 Jordan CJ, Xi ZX. Progress in brain cannabinoid CB2 receptor research: from genes to behavior. Neurosci Biobehav Rev. 2019;98:208-20.
46 Yu SJ, Reiner D, Shen H, Wu KJ, Liu Q-R, Wang Y. Time-dependent protection of CB2 Receptor agonist in stroke. PloS One. 2015;10(7):e0132487.
47 Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153(2):199-215.
48 Glass M, Felder CC. Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors augments cAMP accumulation in striatal neurons: evidence for a Gs linkage to the CB1 receptor. J Neurosci Off J Soc Neurosci. 1997;17(14):5327-33.
49 Rhee MH, Bayewitch M, Avidor-Reiss T, Levy R, Vogel Z. Cannabinoid receptor activation differentially regulates the various adenylyl cyclase isozymes. J Neurochem. 1998;71(4):1525-34.
50 Neubig RR, Spedding M, Kenakin T, Christopoulos A. International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev. 2003;55(4):597-606.
51 May LT, Leach K, Sexton PM, Christopoulos A. Allosteric modulation of G Protein-coupled receptors. Annu Rev Pharmacol Toxicol. 2007;47(1):1-51.
52 Dopart R, Lu D, Lichtman AH, Kendall DA. Allosteric modulators of cannabinoid receptor 1: developing compounds for improved specificity. Drug Metab Rev. 2018;50(1):3-13.
53 Preedy VR, organizador. Handbook of Cannabis and Related Pathologies: Biology, Pharmacology, Diagnosis, and Treatment. 1st ed. London: Academic Press; 2017. 1170p.
54 Janero DR, Thakur GA. Leveraging allostery to improve G protein-coupled receptor (GPCR)-directed therapeutics: cannabinoid receptor 1 as discovery target. Expert Opin Drug Discov. 2016;11(12):1223-37.
55 Roth BL, Irwin JJ, Shoichet BK. Discovery of new GPCR ligands to illuminate new biology. Nat Chem Biol. 2017;13(11):1143-51.
56 Pamplona FA, Ferreira J, Menezes de Lima O Jr, Duarte FS, Bento AF, Forner S, Villarinho JG, Bellocchio L, Wotjak CT, Lerner R, Monory K, Lutz B, Canetti C, Matias I, Calixto JB, Marsicano G, Guimarães MZ, Takahashi RN. Anti-inflammatory lipoxin A4 is an endogenous allosteric enhancer of CB1 cannabinoid receptor. Proc Natl Acad Sci U S A. 2012;109(51):21134-9. Erratum in: Proc Natl Acad Sci U S A. 2013;22;110(4):1561.
57 Vallée M, Vitiello S, Bellocchio L, Hébert-Chatelain E, Monlezun S, Martin-Garcia E, Kasanetz F, Baillie GL, Panin F, Cathala A, Roullot-Lacarrière V, Fabre S, Hurst DP, Lynch DL, Shore DM, Deroche-Gamonet V, Spampinato U, Revest JM, Maldonado R, Reggio PH, Ross RA, Marsicano G, Piazza PV. Pregnenolone can protect the brain from cannabis intoxication. Science. 2014;343(6166):94-8.
58 Petrucci V, Chicca A, Glasmacher S, Paloczi J, Cao Z, Pacher P, Gertsch J. Pepcan-12 (RVD-hemopressin) is a CB2 receptor positive allosteric modulator constitutively secreted by adrenals and in liver upon tissue damage. Sci Rep. 2017;7(1):9560.
59 Gomes I, Grushko JS, Golebiewska U, Hoogendoorn S, Gupta A, Heimann AS, Ferro ES, Scarlata S, Fricker LD, Devi LA. Novel endogenous peptide agonists of cannabinoid receptors. FASEB J. 2009;23(9):3020-9.
60 Maccarrone M. Missing pieces to the endocannabinoid puzzle. Trends Mol Med. 2020;26(3):263-72.
61 Yang H, Zhou J, Lehmann C. GPR55 - a putative “type 3” cannabinoid receptor in inflammation. J Basic Clin Physiol Pharmacol. 2016;27(3):297-302.
62 Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol. 2007;152(7):1092-101.
63 Sharir H, Abood ME. Pharmacological characterization of GPR55, a putative cannabinoid receptor. Pharmacol Ther. 2010;126(3):301-13.
64 Izzo AA, Sharkey KA. Cannabinoids and the gut: new developments and emerging concepts. Pharmacol Ther. 2010;126(1):21-38.
65 Muller C, Morales P, Reggio PH. Cannabinoid ligands targeting TRP channels. Front Mol Neurosci. 2018;11:487.
66 Winter Z, Buhala A, Ötvös F, Jósvay K, Vizler C, Dombi G, Szakonyi G, Oláh Z. Functionally important amino acid residues in the transient receptor potential vanilloid 1 (TRPV1) ion channel - an overview of the current mutational data. Mol Pain. 2013;9-30.
67 Levine JD, Alessandri-Haber N. TRP channels: Targets for the relief of pain. Biochim Biophys Acta. 2007;1772(8):989-1003.
68 Maksim VS, Alexander VZ. TRP Channels as novel targets for endogenous ligands: focus on endocannabinoids and nociceptive signalling. Curr Neuropharmacol. 2018;16(2):137-50.
69 Raboune S, Stuart JM, Leishman E, Takacs SM, Rhodes B, Basnet A, Jameyfield E, McHugh D, Widlanski T, Bradshaw HB. Novel endogenous N-acyl amides activate TRPV1-4 receptors, BV-2 microglia, and are regulated in brain in an acute model of inflammation. Front Cell Neurosci. 2014;8:195.
70 Watanabe H, Vriens J, Prenen J, Droogmans G, Voets T, Nilius B. Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature. 2003;424(6947):434-8.
71 Redmond WJ, Gu L, Camo M, McIntyre P, Connor M. Ligand determinants of fatty acid activation of the pronociceptive ion channel TRPA1. Peer J. 2014;2:e248.
72 De Petrocellis L, Starowicz K, Moriello AS, Vivese M, Orlando P, Di Marzo V. Regulation of transient receptor potential channels of melastatin type 8 (TRPM8): Effect of cAMP, cannabinoid CB1 receptors and endovanilloids. Exp Cell Res. 2007;313(9):1911-20.
73 Alexander SP, Cidlowski JA, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. The Concise Guide to pharmacology 2015/16: nuclear hormone receptors. Br J Pharmacol. 2015;172(24):5956-78.
74 Friedland SN, Leong A, Filion KB, Genest J, Lega IC, Mottillo S, Poirier P, Reoch J, Eisenberg MJ. The cardiovascular effects of peroxisome proliferator-activated receptor agonists. Am J Med. 2012;125(2):126-33.
75 Menendez-Gutierrez MP, Roszer T, Ricote M. Biology and therapeutic applications of peroxisome proliferatoractivated receptors. Curr Top Med Chem. 2012;12(6):548-84.
76 Neher MD, Weckbach S, Huber-Lang MS, Stahel PF. New insights into the role of peroxisome proliferator-activated receptors in regulating the inflammatory response after tissue injury. PPAR Res. 2012;2012:728461.
77 O’Sullivan SE. Cannabinoids go nuclear: evidence for activation of peroxisome proliferator-activated receptors. Br J Pharmacol. 2007;152(5):576-82.
78 O’Sullivan SE. An update on PPAR activation by cannabinoids. Br J Pharmacol. 2016;173(12):1899-910.
79 LoVerme J, La Rana G, Russo R, Calignano A, Piomelli D. The search for the palmitoylethanolamide receptor. Life Sci. 2005;77(14):1685-98.
80 de Novellis V, Luongo L, Guida F, Cristino L, Palazzo E, Russo R, Marabese I, D’Agostino G, Calignano A, Rossi F, Di Marzo V, Maione S. Effects of intra-ventrolateral periaqueductal grey palmitoylethanolamide on thermoceptive threshold and rostral ventromedial medulla cell activity. Eur J Pharmacol. 2012;676(1-3):41-50.
81 Sasso O, Russo R, Vitiello S, Raso GM, D’Agostino G, Iacono A, La Rana G, Vallée M, Cuzzocrea S, Piazza PV, Meli R, Calignano A. Implication of allopregnanolone in the antinociceptive effect of N-palmitoylethanolamide in acute or persistent pain. Pain. 2012;153(1):33-41.
82 Costa B, Comelli F, Bettoni I, Colleoni M, Giagnoni G. The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: involvement of CB(1), TRPV1 and PPARgamma receptors and neurotrophic factors. Pain. 2008;139(3):541-50.
83 Pertwee RG, Howlett AC, Abood ME, Alexander SP, Di Marzo V, Elphick MR, Greasley PJ, Hansen HS, Kunos G, Mackie K, Mechoulam R, Ross RA. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂. Pharmacol Rev. 2010;62(4):588-631.
84 Katona I, Freund TF. Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. Nat Med. 2008;14(9):923-30.
85 Murataeva N, Straiker A, Mackie K. Parsing the players: 2-arachidonoylglycerol synthesis and degradation in the CNS. Br J Pharmacol. 2014;171(6):1379-91.
86 Di Marzo V. New approaches and challenges to targeting the endocannabinoid system. Nat Rev Drug Discov. 2018;17(9):623-39.
87 Cristino L, Bisogno T, Di Marzo V. Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nat Rev Neurol. 2020;16(1):9-29.
88 Pacher P, Bátkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006;58(3):389-462.
89 Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M. Endocannabinoid-mediated control of synaptic transmission. Physiol Rev. 2009;89(1):309-80.
90 Kaczocha M, Glaser ST, Deutsch DG. Identification of intracellular carriers for the endocannabinoid anandamide. Proc Natl Acad Sci. 2009;106(15):6375-80.
91 Oddi S, Fezza F, Pasquariello N, D’Agostino A, Catanzaro G, De Simone C, Rapino C, Finazzi-Agrò A, Maccarrone M. Molecular Identification of Albumin and Hsp70 as Cytosolic Anandamide-Binding Proteins. Chem Biol. 2009;16(6):624-32.
92 Gabrielli M, Battista N, Riganti L, Prada I, Antonucci F, Cantone L, Matteoli M, Maccarrone M, Verderio C. Active endocannabinoids are secreted on extracellular membrane vesicles. EMBO Rep. 2015;16(2):213-20.
93 Nakamura Y, Dryanovski DI, Kimura Y, Jackson SN, Woods AS, Yasui Y, Tsai SY, Patel S, Covey DP, Su TP, Lupica CR. Cocaine-induced endocannabinoid signaling mediated by sigma-1 receptors and extracellular vesicle secretion. Elife. 2019 Oct 9;8:e47209.
94 Castillo PE, Younts TJ, Chávez AE, Hashimotodani Y. Endocannabinoid signaling and synaptic function. Neuron. 2012;76(1):70-81.
95 Ohno-Shosaku T, Kano M. Endocannabinoid-mediated retrograde modulation of synaptic transmission. Curr Opin Neurobiol. 2014;29:1-8.
96 Maccarrone M, Rossi S, Bari M, De Chiara V, Fezza F, Musella A, Gasperi V, Prosperetti C, Bernardi G, Finazzi-Agrò A, Cravatt BF, Centonze D. Anandamide inhibits metabolism and physiological actions of 2-arachidonoylglycerol in the striatum. Nat Neurosci. 2008 Feb;11(2):152-9.
97 Placzek EA, Okamoto Y, Ueda N, Barker EL. Membrane microdomains and metabolic pathways that define anandamide and 2-arachidonyl glycerol biosynthesis and breakdown. Neuropharmacology. 2008;55(7):1095-104.
98 Cravatt BF, Giang DK, Mayfield SP, Boger DL, Lerner RA, Gilula NB. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature. 1996;384(6604):83-7.
99 Di Marzo V. Endocannabinoids: synthesis and degradation. Rev Physiol Biochem Pharmacol. 2008;160:1-24.
100 Jonsson KO, Vandevoorde S, Lambert DM, Tiger G, Fowler CJ. Effects of homologues and analogues of palmitoylethanolamide upon the inactivation of the endocannabinoid anandamide. Br J Pharmacol. 2001;133(8):1263-75.
101 Finn DP, Haroutounian S, Hohmann AG, Krane E, Soliman N, Rice ASC. Cannabinoids, the endocannabinoid system, and pain: a review of preclinical studies. Pain. 2021;162(Suppl 1):S5-25.
102 Dinh TP, Carpenter D, Leslie FM, Freund TF, Katona I, Sensi SL, Kathuria S, Piomelli D. Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci U S A. 2002;99(16):10819-24.
103 Ueda N, Tsuboi K, Uyama T, Ohnishi T. Biosynthesis and degradation of the endocannabinoid 2-arachidonoylglycerol. Bio Factors Oxf Engl. 2011;37(1):1-7.
104 Goparaju SK, Ueda N, Yamaguchi H, Yamamoto S. Anandamide amidohydrolase reacting with 2-arachidonoylglycerol, another cannabinoid receptor ligand. FEBS Lett. 1998;422(1):69-73.
105 Blankman JL, Simon GM, Cravatt BF. A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol. Chem Biol. 2007;14(12):1347-56.
106 Miller MR, Mannowetz N, Iavarone AT, Safavi R, Gracheva EO, Smith JF, Hill RZ, Bautista DM, Kirichok Y, Lishko PV. Unconventional endocannabinoid signaling governs sperm activation via the sex hormone progesterone. Science. 2016;352(6285):555-9.
107 Marrs WR, Blankman JL, Horne EA, Thomazeau A, Lin YH, Coy J, Bodor AL, Muccioli GG, Hu SS, Woodruff G, Fung S, Lafourcade M, Alexander JP, Long JZ, Li W, Xu C, Möller T, Mackie K, Manzoni OJ, Cravatt BF, Stella N. The serine hydrolase ABHD6 controls the accumulation and efficacy of 2-AG at cannabinoid receptors. Nat Neurosci. 2010;13(8):951-7.
108 Navia-Paldanius D, Savinainen JR, Laitinen JT. Biochemical and pharmacological characterization of human α/β-hydrolase domain containing 6 (ABHD6) and 12 (ABHD12). J Lipid Res. 2012;53(11):2413-24.
109 Rouzer CA, Marnett LJ. Endocannabinoid oxygenation by cyclooxygenases, lipoxygenases, and cytochromes P450: cross-talk between the eicosanoid and endocannabinoid signaling pathways. Chem Rev. 2011;111(10):5899-921.
110 Fezza F, Bari M, Florio R, Talamonti E, Feole M, Maccarrone M. Endocannabinoids, related compounds and their metabolic routes. Molecules. 2014;19(11):17078-106.
111 Harayama T, Riezman H. Understanding the diversity of membrane lipid composition. Nat Rev Mol Cell Biol. 2018;19(5):281-96.
112 Dainese E, De Fabritiis G, Sabatucci A, Oddi S, Angelucci CB, Di Pancrazio C, Giorgino T, Stanley N, Del Carlo M, Cravatt BF, Maccarrone M. Membrane lipids are key modulators of the endocannabinoid-hydrolase FAAH. Biochem J. 2014;457(3):463-72.
113 Vanni S, Riccardi L, Palermo G, De Vivo M. Structure and dynamics of the acyl chains in the membrane trafficking and enzymatic processing of lipids. Acc Chem Res. 2019;52(11):3087-96.
Submitted date:
06/15/2022
Accepted date:
02/13/2023