Gastroenterology
Volume 129, Issue 2 , Pages 437-453 , August 2005

Differential Expression of Cannabinoid Receptors in the Human Colon: Cannabinoids Promote Epithelial Wound Healing

  • Karen Wright

      Affiliations

    • Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom
    • Corresponding Author InformationAddress requests for reprints to: Dr. Karen Wright, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom.fax: +44 (0) 1225-386114.
    • ,
  • Nicholas Rooney

      Affiliations

    • Department of Cellular Pathology, Southmead Hospital, Bristol, United Kingdom
    • ,
  • Mark Feeney

      Affiliations

    • Department of Gastroenterology, Royal United Hospital, Bath, United Kingdom
    • ,
  • Jeremy Tate

      Affiliations

    • Department of Gastroenterology, Royal United Hospital, Bath, United Kingdom
    • ,
  • Duncan Robertson

      Affiliations

    • Department of Surgery, Royal United Hospital, Bath, United Kingdom
    • ,
  • Melanie Welham

      Affiliations

    • Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom
    • ,
  • Stephen Ward

      Affiliations

    • Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom

Received 9 July 2004 ,Accepted 13 April 2005.

References 

  1. Gaoni Y , Mechoulam R . Isolation, structure and partial synthesis of an active constituent of hashish . J Am Chem Soc . 1964;86:1646–1647
  2. Devane WA , Dysarz FA , Johnson MR , Melvin LS , Howlett AC . Determination and characterization of a cannabinoid receptor in rat brain . Mol Pharmacol . 1988;34:605–613
  3. Matsuda LA , Lolait SJ , Brownstein MJ , Young AC , Bonner TI . Structure of a cannabinoid receptor and functional expression of the cloned cDNA . Nature . 1990;346:561–564
  4. Munro S , Thomas KL , Abu-Shaar M . Molecular characterization of a peripheral receptor for cannabinoids . Nature . 1993;365:61–65
  5. Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, et al  Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors . Biochem Pharmacol . 1995;50:83–90
  6. Sugiura T, Kondo S, Sukagawa A, Nakane S, Shinoda A, Itoh K, et al. 2-arachidonoylglycerol (a possible endogenous cannabinoid receptor ligand in brain) . Biochem Biophys Res Commun . 1995;215:89–97
  7. Hanus L, Abu-Lafi S, Fride E, Breuer A, Vogel Z, Shalev DE, et al. 2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor . Proc Natl Acad Sci U S A . 2001;98:3662–3665
  8. Porter AC, Sauer JM, Knierman MD, Becker GW, Berna MJ, Bao J, et al. Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor . J Pharmacol Exp Ther . 2002;301:1020–1024
  9. Fowler CJ , Jacobsson SO . Cellular transport of anandamide, 2-arachidonoylglycerol and palmitoylethanolamide—targets for drug development? . Prostaglandins Leukot Essent Fatty Acids . 2002;66:193–200
  10. Sugiura T , Kobayashi Y , Oka S , Waku K . Biosynthesis and degradation of anandamide and 2-arachidonoylglycerol and their possible physiological significance . Prostaglandins Leukot Essent Fatty Acids . 2002;66:173–192
  11. Kozak KR , Marnett LJ . Oxidative metabolism of endocannabinoids . Prostaglandins Leukot Essent Fatty Acids . 2002;66:211–220
  12. Schmid HH , Berdyshev EV . Cannabinoid receptor-inactive N-acylethanolamines and other fatty acid amides (metabolism and function) . Prostaglandins Leukot Essent Fatty Acids . 2002;66:363–376
  13. Merck  . Manual of the materia medica. Rahway, NJ: Merck; 1899;
  14. Grinspoon L , Bakalar JB . Marijuana—the forbidden medicine . New Haven, CT: Yale University Press; 1997;
  15. Dewey WL , Harris LS , Kennedy JS . Some pharmacological and toxicological effects of 1-trans- 8 and 1-trans-9-tetrahydrocannabinol in laboratory rodents . Arch Int Pharmacodyn Ther . 1972;196:133–145
  16. Coupar IM , Taylor DA . Effect of delta 9-tetrahydrocannabinol on prostaglandin concentrations and fluid absorption rates in the rat small intestine . J Pharm Pharmacol . 1983;35:392–394
  17. Sofia RD , Diamantis W , Edelson J . Effect of delta9-tetrahydrocannabinol on the gastrointestinal tract of the rat . Pharmacology . 1978;17:79–82
  18. Chesher GB , Dahl CJ , Everingham M , Jackson DM , Marchant-Williams H , Starmer GA . The effect of cannabinoids on intestinal motility and their antinociceptive effect in mice . Br J Pharmacol . 1973;49:588–594
  19. Kulkarni-Narla A , Brown DR . Localization of CB1-cannabinoid receptor immunoreactivity in the porcine enteric nervous system . Cell Tissue Res . 2000;302:73–80
  20. Coutts AA , Irving AJ , Mackie K , Pertwee RG , Anavi-Goffer S . Localisation of cannabinoid CB(1) receptor immunoreactivity in the guinea pig and rat myenteric plexus . J Comp Neurol . 2002;448:410–422
  21. Casu MA, Porcella A, Ruiu S, Saba P, Marchese G, Carai MA, et al. Differential distribution of functional cannabinoid CB1 receptors in the mouse gastroenteric tract . Eur J Pharmacol . 2003;459:97–105
  22. MacNaughton WK , Van Sickle MD , Keenan CM , Cushing K , Mackie K , Sharkey KA . Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum (relationship to capsaicin-sensitive nerves) . Am J Physiol Gastrointest Liver Physiol . 2004;286:G863–G871
  23. Storr M, Sibaev A, Marsicano G, Lutz B, Schusdziarra V, Timmermans JP, et al. Cannabinoid receptor type 1 modulates excitatory and inhibitory neurotransmission in mouse colon . Am J Physiol . 2004;286:G110–G117
  24. Croci T, Manara L, Aureggi G, Guagnini F, Rinaldi-Carmona M, Maffrand JP, et al. In vitro functional evidence of neuronal cannabinoid CB1 receptors in human ileum . Br J Pharmacol . 1998;125:1393–1395
  25. Pinto L, Izzo AA, Cascio MG, Bisogno T, Hospodar-Scott K, Brown DR, et al. Endocannabinoids as physiological regulators of colonic propulsion in mice . Gastroenterology . 2002;123:227–234
  26. Izzo AA, Fezza F, Capasso R, Bisogno T, Pinto L, Iuvone T, et al. Cannabinoid CB1-receptor mediated regulation of gastrointestinal motility in mice in a model of intestinal inflammation . Br J Pharmacol . 2001;134:563–570
  27. McVey DC , Schmid PC , Schmid HH , Vigna SR . Endocannabinoids induce ileitis in rats via the capsaicin receptor (VR1) . J Pharmacol Exp Ther . 2003;304:713–722
  28. Ligresti A, Bisogno T, Matias I, De Petrocellis L, Cascio MG, Cosenza V, et al. Possible endocannabinoid control of colorectal cancer growth . Gastroenterology . 2003;125:677–687
  29. Manara L, Croci T, Guagnini F, Rinaldi-Carmona M, Maffrand JP, Le Fur G, et al. Functional assessment of neuronal cannabinoid receptors in the muscular layers of human ileum and colon . Dig Liver Dis . 2002;34:262–269
  30. Mascolo N, Izzo AA, Ligresti A, Costagliola A, Pinto L, Cascio MG, et al. The endocannabinoid system and the molecular basis of paralytic ileus in mice . FASEB J . 2002;16:1973–1975
  31. Landi M , Croci T , Rinaldi-Carmona M , Maffrand JP , Le Fur G , Manara L . Modulation of gastric emptying and gastrointestinal transit in rats through intestinal cannabinoid CB(1) receptors . Eur J Pharmacol . 2002;450:77–83
  32. Izzo AA, Capasso F, Costagliola A, Bisogno T, Marsicano G, Ligresti A, et al. An endogenous cannabinoid tone attenuates cholera toxin-induced fluid accumulation in mice . Gastroenterology . 2003;125:765–774
  33. Begg M , Dale N , Llaudet E , Molleman A , Parsons ME . Modulation of the release of endogenous adenosine by cannabinoids in the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum . Br J Pharmacol . 2002;137:1298–1304
  34. Mang CF , Erbelding D , Kilbinger H . Differential effects of anandamide on acetylcholine release in the guinea-pig ileum mediated via vanilloid and non-CB1 cannabinoid receptors . Br J Pharmacol . 2001;134:161–167
  35. Galiegue S, Mary S, Marchand J, Dussossoy D, Carriere D, Carayon P, et al. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations . Eur J Biochem . 1995;232:54–61
  36. Griffin G, Fernando SR, Ross RA, McKay NG, Ashford ML, Shire D, et al. Evidence for the presence of CB2-like cannabinoid receptors on peripheral nerve terminals . Eur J Pharmacol . 1997;339:53–61
  37. Mathison R , Ho W , Pittman QJ , Davison JS , Sharkey KA . Effects of cannabinoid receptor-2 activation on accelerated gastrointestinal transit in lipopolysaccharide-treated rats . Br J Pharmacol . 2004;142:1247–1254
  38. Berdyshev EV . Cannabinoid receptors and the regulation of immune response . Chem Phys Lipids . 2000;108:169–190
  39. Roth MD , Baldwin GC , Tashkin DP . Effects of delta-9-tetrahydrocannabinol on human immune function and host defense . Chem Phys Lipids . 2002;121:229–239
  40. Bhat NR , Zhang P , Hogan EL . Thrombin activates mitogen-activated protein kinase in primary astrocyte cultures . J Cell Physiol . 1995;165:417–424
  41. Bouaboula M, Poinot-Chazel C, Bourrie B, Canat X, Calandra B, Rinaldi-Carmona M, et al. Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1 . Biochem J . 1995;312:637–641
  42. Bouaboula M, Perrachon S, Milligan L, Canat X, Rinaldi-Carmona M, Portier M, et al. A selective inverse agonist for central cannabinoid receptor inhibits mitogen-activated protein kinase activation stimulated by insulin or insulin-like growth factor 1. Evidence for a new model of receptor/ligand interactions . J Biol Chem . 1997;272:22330–22339
  43. Gomez del Pulgar T , Velasco G , Guzman M . The CB1 cannabinoid receptor is coupled to the activation of protein kinase B/Akt . Biochem J . 2000;347:369–373
  44. Molina-Holgado E, Vela JM, Arevalo-Martin A, Almazan G, Molina-Holgado F, Borrell J, et al. Cannabinoids promote oligodendrocyte progenitor survival (involvement of cannabinoid receptors and phosphatidylinositol-3 kinase/Akt signaling) . J Neurosci . 2002;22:9742–9753
  45. Sutherland C , Leighton IA , Cohen P . Inactivation of glycogen synthase kinase-3 beta by phosphorylation (new kinase connections in insulin and growth-factor signalling) . Biochem J . 1993;296:15–19
  46. Sutherland C , Cohen P . The alpha-isoform of glycogen synthase kinase-3 from rabbit skeletal muscle is inactivated by p70 S6 kinase or MAP kinase-activated protein kinase-1 in vitro . FEBS Lett . 1994;338:37–42
  47. Cross DA , Alessi DR , Cohen P , Andjelkovich M , Hemmings BA . Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B . Nature . 1995;378:785–789
  48. Wheater PR , Burkitt HG , Daniels VG. Functional histology . London, UK: Churchill Livingstone; 1979;
  49. Massa F, Marsicano G, Hermann H, Cannich A, Monory K, Cravatt BF, et al. The endogenous cannabinoid system protects against colonic inflammation . J Clin Invest . 2004;113:1202–1209
  50. Pettit DA , Harrison MP , Olson JM , Spencer RF , Cabral GA . Immunohistochemical localization of the neural cannabinoid receptor in rat brain . J Neurosci Res . 1998;51:391–402
  51. Song C , Howlett AC . Rat brain cannabinoid receptors are N-linked glycosylated proteins . Life Sci . 1995;56:1983–1989
  52. Carayon P, Marchand J, Dussossoy D, Derocq JM, Jbilo O, Bord A, et al. Modulation and functional involvement of CB2 peripheral cannabinoid receptors during B-cell differentiation . Blood . 1998;92:3605–3615
  53. Rouzer CA , Ghebreselasie K , Marnett LJ . Chemical stability of 2-arachidonylglycerol under biological conditions . Chem Phys Lipids . 2002;119:69–82
  54. Podolsky DK . Inflammatory bowel disease . N Engl J Med . 2002;347:417–429
  55. Sturm A , Dignass AU . Modulation of gastrointestinal wound repair and inflammation by phospholipids . Biochim Biophys Acta . 2002;1582:282–288
  56. Sturm A , Sudermann T , Schulte KM , Goebell H , Dignass AU . Modulation of intestinal epithelial wound healing in vitro and in vivo by lysophosphatidic acid . Gastroenterology . 1999;117:368–377
  57. Shida D, Kitayama J, Yamaguchi H, Okaji Y, Tsuno NH, Watanabe T, et al. Lysophosphatidic acid (LPA) enhances the metastatic potential of human colon carcinoma DLD1 cells through LPA1 . Cancer Res . 2003;63:1706–1711
  58. Calignano A , La Rana G , Makriyannis A , Lin SY , Beltramo M , Piomelli D . Inhibition of intestinal motility by anandamide, an endogenous cannabinoid . Eur J Pharmacol . 1997;340:R7–R8
  59. Izzo AA , Mascolo N , Pinto L , Capasso R , Capasso F . The role of cannabinoid receptors in intestinal motility, defaecation and diarrhoea in rats . Eur J Pharmacol . 1999;384:37–42
  60. Cota D, Marsicano G, Lutz B, Vicennati V, Stalla GK, Pasquali R, et al. Endogenous cannabinoid system as a modulator of food intake . Int J Obes Relat Metab Disord . 2003;27:289–301
  61. Pinto L , Capasso R , Di Carlo G , Izzo AA . Endocannabinoids and the gut . Prostaglandins Leukot Essent Fatty Acids . 2002;66:333–341
  62. Gomez R, Navarro M, Ferrer B, Trigo JM, Bilbao A, Del Arco I, et al. A peripheral mechanism for CB1 cannabinoid receptor-dependent modulation of feeding . J Neurosci . 2002;22:9612–9617
  63. Croci T , Landi M , Galzin AM , Marini P . Role of cannabinoid CB1 receptors and tumor necrosis factor-alpha in the gut and systemic anti-inflammatory activity of SR 141716 (Rimonabant) in rodents . Br J Pharmacol . 2003;140:115–122
  64. Swidsinski A, Ladhoff A, Pernthaler A, Swidsinski S, Loening-Baucke V, Ortner M, et al. Mucosal flora in inflammatory bowel disease . Gastroenterology . 2002;122:44–54
  65. Panja A , Siden E , Mayer L . Synthesis and regulation of accessory/proinflammatory cytokines by intestinal epithelial cells . Clin Exp Immunol . 1995;100:298–305
  66. Ihenetu K , Molleman A , Parsons ME , Whelan CJ . Inhibition of interleukin-8 release in the human colonic epithelial cell line HT-29 by cannabinoids . Eur J Pharmacol . 2003;458:207–215
  67. Mahida YR , Ceska M , Effenberger F , Kurlak L , Lindley I , Hawkey CJ . Enhanced synthesis of neutrophil-activating peptide-1/interleukin-8 in active ulcerative colitis . Clin Sci (Lond) . 1992;82:273–275
  68. Sanchez MG , Ruiz-Llorente L , Sanchez AM , Diaz-Laviada I . Activation of phosphoinositide 3-kinase/PKB pathway by CB(1) and CB(2) cannabinoid receptors expressed in prostate PC-3 cells. Involvement in Raf-1 stimulation and NGF induction . Cell Signal . 2003;15:851–859
  69. Samson MT , Small-Howard A , Shimoda LM , Koblan-Huberson M , Stokes AJ , Turner H . Differential roles of CB1 and CB2 cannabinoid receptors in mast cells . J Immunol . 2003;170:4953–4962
  70. Shi C, Szczesniak A, Mao L, Jollimore C, Coca-Prados M, Hung O, et al. A3 adenosine and CB1 receptors activate a PKC-sensitive Cl- current in human nonpigmented ciliary epithelial cells via a G beta gamma-coupled MAPK signaling pathway . Br J Pharmacol . 2003;139:475–486
  71. Upham BL, Rummel AM, Carbone JM, Trosko JE, Ouyang Y, Crawford RB, et al. Cannabinoids inhibit gap junctional intercellular communication and activate ERK in a rat liver epithelial cell line . Int J Cancer . 2003;104:12–18
  72. Pertwee RG . Inverse agonism and neutral antagonism at cannabinoid CB(1) receptors . Life Sci . 2005;76:1307–1324
  73. Molderings GJ , Bonisch H , Hammermann R , Gothert M , Bruss M . Noradrenaline release-inhibiting receptors on PC12 cells devoid of alpha(2(-)) and CB(1) receptors (similarities to presynaptic imidazoline and edg receptors) . Neurochem Int . 2002;40:157–167
  74. Bouaboula M , Desnoyer N , Carayon P , Combes T , Casellas P . Gi protein modulation induced by a selective inverse agonist for the peripheral cannabinoid receptor CB2 (implication for intracellular signalization cross-regulation) . Mol Pharmacol . 1999;55:473–480
  75. Hiley CR , Ford WR . Cannabinoid pharmacology in the cardiovascular system (potential protective mechanisms through lipid signalling) . Biol Rev Camb Philos Soc . 2004;79:187–205
  76. Matsubayashi Y , Ebisuya M , Honjoh S , Nishida E . ERK activation propagates in epithelial cell sheets and regulates their migration during wound healing . Curr Biol . 2004;14:731–735
  77. Roberts MS , Woods AJ , Shaw PE , Norman JC . ERK1 associates with alpha(v)beta 3 integrin and regulates cell spreading on vitronectin . J Biol Chem . 2003;278:1975–1985
  78. Roberts MS , Woods AJ , Dale TC , Van Der Sluijs P , Norman JC . Protein kinase B/Akt acts via glycogen synthase kinase 3 to regulate recycling of alpha v beta 3 and alpha 5 beta 1 integrins . Mol Cell Biol . 2004;24:1505–1515
  79. Etienne-Manneville S , Hall A . Cdc42 regulates GSK-3beta and adenomatous polyposis coli to control cell polarity . Nature . 2003;421:753–756

 Supported by a Wellcome Trust and National Health Service research grant, United Kingdom.

PII: S0016-5085(05)00929-7

doi: 10.1053/j.gastro.2005.05.026

Gastroenterology
Volume 129, Issue 2 , Pages 437-453 , August 2005

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