The endocannabinoid system in advanced liver cirrhosis: Pathophysiological implication and future perspectives

Liver International

Volumn 33, Issue 9, 2013, Pages 1298-1308

  Baldassarre, Maurizio ^a   Giannone, Ferdinando A ^a   Napoli, Lucia ^a   Tovoli, Alessandra ^a   Ricci, Carmen S ^a   Tufoni, Manuel ^a   Caraceni, Paolo ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

Ascites; CB1 receptor; CB2 receptor; Cirrhotic cardiomyopathy; Endocannabinoids; Hyperdynamic circulatory syndrome; Liver cirrhosis

Indexed keywords

2 METHYL 3 (1 NAPHTHOYL) 1 PROPYLINDOLE; 4 [4 (1,1 DIMETHYLHEPTYL) 2,6 DIMETHOXYPHENYL] 6,6 DIMETHYLBICYCLO[3.1.1]HEPT 2 EN 2 YLMETHANOL; CP 945 598; ENDOCANNABINOID; OTENABANT; RIMONABANT; TARANABANT; UNCLASSIFIED DRUG;

ARTICLE; ASCITES; BACTERIAL INFECTION; CARDIOMYOPATHY; HEPATIC ENCEPHALOPATHY; HUMAN; LIVER CIRRHOSIS; LIVER FIBROSIS; PATHOPHYSIOLOGY; PORTAL HYPERTENSION; SODIUM RETENTION; VASCULAR RESISTANCE;

ASCITES; CB1 RECEPTOR; CB2 RECEPTOR; CIRRHOTIC CARDIOMYOPATHY; ENDOCANNABINOIDS; HYPERDYNAMIC CIRCULATORY SYNDROME; LIVER CIRRHOSIS;

CANNABINOID RECEPTOR ANTAGONISTS; ENDOCANNABINOIDS; GENE EXPRESSION REGULATION; HUMANS; LIVER CIRRHOSIS; MODELS, BIOLOGICAL; PIPERIDINES; PYRAZOLES; RECEPTORS, CANNABINOID; SIGNAL TRANSDUCTION;

EID: 84883760532     PISSN: 14783223     EISSN: 14783231     Source Type: Journal    
DOI: 10.1111/liv.12263     Document Type: Article

References (101)

1. Pacher P, Batkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 2006; 58: 389-462.
2. Gaoni Y, Mechoulam M. Isolation, structure, and partial synthesis of an active constituent of hashish. J Am Chem Soc 1964; 86: 1646-7.
3. Di Marzo V. The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov 2008; 7: 438-55.
4. De Petrocellis L, Di Marzo V. An introduction to the endocannabinoid system: from the early to the latest concepts. Best Pract Res Clin Endocrinol Metab 2009; 23: 1-15.
5. Mechoulam R, Gaoni Y. The absolute configuration of delta-1-tetrahydrocannabinol, the major active constituent of hashish. Tetrahedron Lett 1967; 12: 1109-11.
6. Devane WA, Dysarz FA 3rd, Johnson MR, Melvin LS, Howlett AC. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 1988; 34: 605-13.
7. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990; 346: 561-4.
8. Butler H, Korbonits M. Cannabinoids for clinicians the rise and fall of the cannabinoid antagonists. Eur J Endocrinol 2009; 161: 655-62.
9. Mackie K. Mechanisms of CB1 receptor signaling: endocannabinoid modulation of synaptic strength. Int J Obes (Lond) 2006; 30(Suppl. 1): S19-23.
10. Galiegue S, Mary S, Marchand J, et al. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem 1995; 232: 54-61.
11. Pagotto U, Marsicano G, Cota D, Lutz B, Pasquali R. The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr Rev 2006; 27: 73-100.
12. Mackie K, Stella N. Cannabinoid receptors and endocannabinoids: evidence for new players. AAPS J 2006; 8: 298-306.
13. Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993; 365: 61-5.
14. Gong JP, Onaivi ES, Ishiguro H, et al. Cannabinoid CB2 receptors: immunohistochemical localization in rat brain. Brain Res 2006; 1071: 10-23.
15. Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992; 258: 1946-9.
16. Mechoulam R, Ben-Shabat S, Hanus L, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 1995; 50: 83-90.
17. Sugiura T, Kondo S, Sukagawa A, et al. 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun 1995; 215: 89-97.
18. Hillard CJ, Jarrahian A. The movement of N-arachidonoylethanolamine (anandamide) across cellular membranes. Chem Phys Lipids 2000; 108: 123-34.
19. De Petrocellis L, Di Marzo V. Non-CB1, non-CB2 receptors for endocannabinoids, plant cannabinoids, and synthetic cannabimimetics: focus on G-protein-coupled receptors and transient receptor potential channels. J Neuroimmune Pharmacol 2010; 5: 103-21.
20. Bisogno T, Ligresti A, Di Marzo V. The endocannabinoid signalling system: biochemical aspects. Pharmacol Biochem Behav 2005; 81: 224-38.
21. Ryberg E, Larsson N, Sjögren S, et al. The orphan receptor gpr55 is a novel cannabinoid receptor. Br J Pharmacol 2007; 152: 1092-101.
22. Alexander SP, Kendall DA. The complications of promiscuity: endocannabinoid action and metabolism. Br J Pharmacol 2007; 152: 602-23.
23. Teixeira-Clerc F, Julien B, Grenard P, et al. CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis. Nat Med 2006; 12: 671-6.
24. Buckley NE, Hansson S, Harta G, Mezey E. Expression of the CB1 and CB2 receptor messenger RNAs during embryonic development in the rat. Neuroscience 1998; 82: 1131-49.
25. Mallat A, Lotersztajn S. Endocannabinoids and liver disease. Endocannabinoids and their receptors in the liver. Am J Gastrointest Liver Physiol 2008; 294: 9-12.
26. Caraceni P, Pertosa AM, Giannone F, et al. Antagonism of the cannabinoid CB-1 receptor protects rat liver against ischaemia-reperfusion injury complicated by endotoxaemia. Gut 2009; 58: 1135-43.
27. Siegmund SV, Qian T, De Minicis S, et al. The endocannabinoid 2-arachidonyl glycerol induces death of hepatic stellate cells via mitochondrial oxygen species. FASEB J 2007; 21: 2798-806.
28. Cao Z, Mulvihill MM, Mukhopadhyay P, et al. Monoacylglycerol lipase controls endocannabinoid and eicosanoid signaling and hepatic injury in mice. Gastroenterology 2013; 144: 808-17.
29. Batkai S, Jarai Z, Wagner JA, et al. Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis. Nat Med 2001; 7: 827-32.
30. Fernández-Rodriguez CM, Romero J, Petros TJ, et al. Circulating endogenous cannabinoid anandamide and portal, systemic and renal hemodynamics in cirrhosis. Liver Int 2004; 24: 477-83.
31. Caraceni P, Viola A, Piscitelli F, et al. Circulating and hepatic endocannabinoids and endocannabinoid-related molecules in patients with cirrhosis. Liver Int 2010; 30: 816-25.
32. Bosch J, Berzigotti A, Garcia-Pagan JC, Abraldes JG. The management of portal hypertension: rational basis, available treatments and future options. J Hepatol 2008; 48(Suppl. 1): S68-92.
33. Lotersztajn S, Julien B, Teixeira-Clerc F, Grenard P, Mallat A. Hepatic fibrosis: molecular mechanism and drug targets. Annu Rev Pharmacol Toxicol 2005; 45: 605-28.
34. Hezode C, Roudot-Thoraval F, Nguyen S, et al. Daily cannabis smoking as a risk factor for progression of fibrosis in chronic hepatitis C. Hepatology 2005; 42: 63-71.
35. Caraceni P, Domenicali M, Giannone F, Bernardi M. The role of the endocannabinoid system in liver diseases. Best Pract Res Clin Endocrinol Metab 2009; 23: 65-77.
36. Giannone FA, Baldassarre M, Domenicali M, et al. Reversal of liver fibrosis by the antagonism of endocannabinoid CB1 receptor in a rat model of CCl(4)-induced advanced cirrhosis. Lab Invest 2012; 92: 384-95.
37. Julien B, Grenard P, Texeira-Clerc F, et al. Antifibrogenic role of the cannabinoid receptor CB2 in the liver. Gastroenterology 2005; 128: 742-55.
38. Teixeira-Clerc F, Belot MP, Manin S, et al. Beneficial paracrine effects of cannabinoid receptor 2 on liver injury and regeneration. Hepatology 2010; 52: 1046-59.
39. 4-treated rats: role of the hepatic endocannabinoid and apelin systems. J Pharmacol Exp Ther 2012; 340: 629-37.
40. Rossi F, Bellini G, Alisi A, et al. Cannabinoid receptor type 2 functional variant influences liver damage in children with non-alcoholic Fatty liver disease. PLoS ONE 2012; 7: 42259.
41. Domenicali M, Caraceni P, Giannone F, et al. Cannabinoid type 1 receptor antagonism delays ascites formation in rats with cirrhosis. Gastroenterology 2009; 137: 341-9.
42. Munoz-Luque J, Ros J, Fernandez-Varo G, et al. Regression of fibrosis after chronic stimulation of cannabinoid CB2 receptor in cirrhotic rats. J Pharmacol Exp Ther 2008; 324: 475-83.
43. Yang YY, Lin HC, Huang YT, et al. Roles of anandamide in the hepatic microcirculation in cirrhotic rats. Am J Physiol Gastrointest Liver Physiol 2005; 290: 328-34.
44. Yang YY, Lin HC, Huang YT, et al. Effect of chronic CB1 receptor antagonism on livers of rats with biliary cirrhosis. Clin Sci 2007; 112: 533-42.
45. Schrier RW, Arroyo V, Bernardi M, et al. Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology 1988; 8: 1151-7.
46. Iwakiri Y, Groszmann RJ. The hyperdynamic circulation of chronic liver diseases: from the patient to the molecule. Hepatology 2006; 43(Suppl. 1): S121-31.
47. Ros J, Claria J, To-Figueras J, et al. Endogenous cannabinoids: a new system involved in the homeostasis of arterial pressure in experimental cirrhosis in the rat. Gastroenterology 2002; 122: 85-93.
48. Varga K, Wagner JA, Bridgen DT, Kunos G. Platelet and macrophages derived endogenous cannabinoid are involved in endotoxine induced hypotension. FASEB J 1998; 12: 1035-44.
49. Maccarrone M, De Petrocellis L, Bari M, et al. Lipopolysaccharide downregulates fatty acid amide hydrolase expression and increases anandamide levels in human peripheral lymphocytes. Arch Biochem Biophys 2001; 393: 321-8.
50. Liu J, Batkai S, Pacher P, et al. Lipopolysaccharide induces anandamide synthesis in macrophages via CD14/MAPK/phosphoinositide 3-kinase/NF-kappaB independently of platelet-activating factor. J Biol Chem 2003; 278: 45034-9.
51. Maccarrone M, Bari M, Battista N, Finazzi-Agrò A. Endocannabinoid degradation, endotoxic shock and inflammation. Curr Drug Targets Inflamm Allergy 2002; 1: 53-63.
52. Domenicali M, Ros J, Fernández-Varo G, et al. Increased anandamide induced relaxation in mesenteric arteries of cirrhotic rats: role of cannabinoid and vanilloid receptors. Gut 2005; 54: 522-7.
53. Ralevic V, Kendall DA, Randall MD, Smart D. Cannabinoid modulation of sensory neurotransmission via cannabinoid and vanilloid receptors: roles in regulation of cardiovascular function. Life Sci 2002; 71: 2577-94.
54. Moezi L, Gaskari SA, Liu H, et al. Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB(1) and VR(1) receptors. Br J Pharmacol 2006; 149: 898-908.
55. Orliac ML, Peroni R, Celuch SM, Adler-Graschinsky E. Potentiation of anandamide effects in mesenteric beds isolated from endotoxemic rats. J Pharmacol Exp Ther 2003; 304: 179-84.
56. Bernardi M, Colantoni A, Caraceni P, Sica G, Trevisani F. Natural course and physiopathology of ascites in the cirrhotic patient. Ann Ital Med Int 1996; 11(Suppl. 2): S30-8.
57. Song D, Liu H, Sharkey KA, Lee SS. Hyperdynamic circulation in portal-hypertensive rats is dependent on central c-fos gene expression. Hepatology 2002; 35: 159-66.
58. Pacher P, Bàtkai S, Kunos G. Cirrhotic cardiomyopathy: an endocannabinoid connection? Br J Pharmacol 2005; 146: 313-4.
59. Ma Z, Lee SS. Cirrhotic cardiomyopathy: getting to the heart of the matter. Hepatology 1996; 24: 451-9.
60. Møller S, Henriksen JH. Cirrhotic cardiomyopathy: a pathophysiological review of circulatory dysfunction in liver disease. Heart 2002; 87: 9-15.
61. Malinowska B, Lupinski S, Godlewski G, Baranowska U, Schlicker E. Role endocannabinoids in cardiovascular shock. J Physiol Pharmacol 2008; 59(Suppl. 8): S91-107.
62. Gaskari SA, Honar H, Lee SS. Therapy insight: cirrhotic cardiomyopathy. Nat Clin Pract Gastroenterol Hepatol 2006; 3: 329-37.
63. Gaskari SE, Liu H, Moezi L, et al. Role of endocannabinoids in the pathogenesis of cirrhotic cardiomiopathy in bile duct-ligated rats. Br J Pharmacol 2005; 146: 315-23.
64. Gebremedhin D, Lange AR, Campbell WB, Hillard CJ, Harder DR. Cannabinoid CB1 receptor of cat cerebral arterial muscle functions to inhibit L-type Ca2+ channel current. Am J Physiol 1999; 276: H2085-93.
65. Howlett AC, Bidaut-Russell M, Devane WA, et al. The cannabinoid receptor: biochemical, anatomical and behavioral characterization. Trends Neurosci 1990; 13: 420-3.
66. Bátkai S, Mukhopadhyay P, Harvey-White J, et al. Endocannabinoids acting at CB1 receptors mediate the cardiac contractile dysfunction in vivo in cirrhotic rats. Am J Physiol Heart Circ Physiol 2007; 293: H1689-95.
67. Yang YY, Liu H, Nam SW, Kunos G, Lee SS. Mechanism of TNFalpha-induced cardiac dysfunction in cholestatic bile duct-ligated mice: interaction between TNFalpha and endocannabinoids. J Hepatol 2010; 53: 298-306.
68. Magen I, Avraham Y, Berry E, Mechoulam R. Endocannabinoids in liver disease and hepatic encephalopathy. Curr Pharm Des 2008; 14: 2362-9.
69. Avraham Y, Israeli E, Gabbay E, et al. Endocannabinoids affect neurological and cognitive function in thioacetamide-induced hepatic encephalopathy in mice. Neurobiol Dis 2006; 21: 237-45.
70. Dagon Y, Avraham Y, Ilan Y, Mechoulam R, Berry EM. Cannabinoids ameliorate cerebral dysfunction following liver failure via AMP-activated protein kinase. FASEB J 2007; 21: 2431-41.
71. Huang L, Quinn MA, Frampton GA, Golden LE, DeMorrow S. Recent advances in the understanding of the role of the endocannabinoid system in liver diseases. Dig Liver Dis 2011; 43: 188-93.
72. Avraham Y, Zolotarev O, Grigoriadis NC, et al. Cannabinoids and capsaicin improve liver function following thioacetamide-induced acute injury in mice. Am J Gastroenterol 2008; 103: 3047-56.
73. Magen I, Avraham Y, Ackerman Z, et al. Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation. J Hepatol 2009; 51: 528-34.
74. Magen I, Avraham Y, Ackerman Z, et al. Cannabidiol ameliorates cognitive and motor impairments in bile-duct ligated mice via 5-HT1A receptor activation. Br J Pharmacol 2010; 159: 950-7.
75. Avraham Y, Grigoriadis N, Poutahidis T, et al. Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice. Br J Pharmacol 2011; 162: 1650-8.
76. Fernández J, Gustot T. Management of bacterial infections in cirrhosis. J Hepatol 2012; 56(Suppl. 1): S1-12.
77. Maccarrone M, Fiorucci L, Erba F, et al. Human mast cells take up and hydrolyze anandamide under the control of 5 lipoxygenase and do not express endocannabinoidi receptors. FEBS Lett 2000; 468: 176-80.
78. Lin HC, Yang YY, Tsai TH, et al. The relationship between endotoxinemia and hepatic endocannabinoids in cirrhotic rats with portal hypertension. J Hepatol 2011; 54: 1145-53.
79. Domenicali M, Giannone FA, Baldassarre M, et al. Protective effect of a cannabinoid CB1-receptor antagonist in a rat model of cirrhosis complicated by sepsis. Hepatology 2009; 50(Suppl. 4): S335-6.
80. Reichenbach V, Muñoz-Luque J, Ros J, et al. Bacterial lipopolyshaccaride inhibits CB2 receptor expression in human monocytic cells. Gut 2013; 62: 1089-91.
81. Wagner JA, Varga K, Ellis EF, et al. Activation of peripheral CB1 receptors in hemorrhagic shock. Nature 1997; 390: 518-21.
82. Silvestri C, Di Marzo V. Second generation CB1 receptor blockers and other inhibitors of peripheral endocannabinoid overactivity and the rationale of their use against metabolic disorders. Expert Opin Investig Drugs 2012; 21: 1309-22.
83. Burstein SH, Zurier RB. Cannabinoids, endocannabinoids, and related analogs in inflammation. AAPS J 2009; 11: 109-19.
84. Scheen AJ, Finer N, Hollander P, Jensen MD, Van Gaal LF; RIO-Diabetes Study Group. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet 2006; 368: 1660-72.
85. Xie S, Furjanic MA, Ferrara JJ, et al. The endocannabinoid system and rimonabant: a new drug with a novel mechanism of action involving cannabinoid CB1 receptor antagonism - or inverse agonism - as potential obesity treatment and other therapeutic use. J Clin Pharm Ther 2007; 32: 209-31.
86. Moreira FA, Crippa JA. The psychiatric side-effects of rimonabant. Rev Bras Psiquiatr 2009; 31: 145-53.
87. Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J; RIO-North America Study Group. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA 2006; 295: 761-75.
88. Van Gaal L, Pi-Sunyer X, Després JP, McCarthy C, Scheen A. Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients: pooled 1-year data from the Rimonabant in Obesity (RIO) program. Diabetes Care 2008; 31(Suppl. 2): S229-40.
89. Fong TM, Guan XM, Marsh DJ, et al. Antiobesity efficacy of a novel cannabinoid-1 receptor inverse agonist, N-((1S, 2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl)-2-methyl-2-((5-(trifluoromethyl)pyridin-2-yl)oxy)propanamide (MK-0364), in rodents. J Pharmacol Exp Ther 2007; 321: 1013-22.
90. Aronne LJ, Finer N, Hollander PA, et al. Efficacy and safety of CP-945, 598, a selective cannabinoid CB1 receptor antagonist, on weight loss and maintenance. Obesity (Silver Spring) 2011; 19: 1404-14.
91. Cunha P, Romão AM, Mascarenhas-Melo F, Teixeira HM, Reis F. Endocannabinoid system in cardiovascular disorders - new pharmacotherapeutic opportunities. J Pharm Bioallied Sci 2011; 3: 350-60.
92. Mallat A, Teixeira-Clerc F, Deveaux V, Manin S, Lotersztajn S. The endocannabinoid system as a key mediator during liver diseases: new insights and therapeutic openings. Br J Pharmacol 2011; 163: 1432-40.
93. Fulp A, Bortoff K, Zhang Y, et al. Towards rational design of cannabinoid receptor 1 (CB1) antagonists for peripheral selectivity. Bioorg Med Chem Lett 2011; 21: 5711-4.
94. Tam J, Cinar R, Liu J, et al. Peripheral cannabinoid-1 receptor inverse agonism reduces obesity by reversing leptin resistance. Cell Metab 2012; 16: 167-79.
95. Tam J, Vemuri VK, Liu J, et al. Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity. J Clin Invest 2010; 120: 2953-66.
96. Randall PA, Vemuri VK, Segovia KN, et al. The novel cannabinoid CB1 antagonist AM6545 suppresses food intake and food-reinforced behavior. Pharmacol Biochem Behav 2010; 97: 179-84.
97. Cluny NL, Vemuri VK, Chambers AP, et al. A novel peripherally restricted cannabinoid receptor antagonist, AM6545, reduces food intake and body weight, but does not cause malaise, in rodents. Br J Pharmacol 2010; 161: 629-42.
98. Steffens S, Pacher P. Targeting cannabinoid receptor CB(2) in cardiovascular disorders: promises and controversies. Br J Pharmacol 2012; 167: 313-23.
99. Montecucco F, Burger F, Mach F, Steffens S. CB2 cannabinoid receptor agonist JWH-015 modulates human monocyte migration through defined intracellular signaling pathways. Am J Physiol Heart Circ Physiol 2008; 294: 1145-55.
100. Ofek O, Karsak M, Leclerc N, et al. Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc Natl Acad Sci USA 2006; 103: 696-701.
101. Palumbo-Zerr K, Horn A, Distler A, et al. Inactivation of fatty acid amide hydrolase exacerbates experimental fibrosis by enhanced endocannabinoid-mediated activation of CB1. Ann Rheum Dis 2012; 71: 2051-4.