Skip to main content
SpringerLink
Log in

Novel Anti-inflammatory and Vasodilatory ω-3 Endocannabinoid Epoxide Regioisomers

  • Chapter
  • First Online:
The Role of Bioactive Lipids in Cancer, Inflammation and Related Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1161))

Abstract

Accumulating evidence suggests that diets rich in ω-3 polyunsaturated fatty acids (PUFAs) offer protection against vascular inflammation, neuroinflammation, hypertension, and thrombosis. Recently, biochemical studies have demonstrated that these benefits are partially mediated by their conversion to ω-3 endocannabinoid epoxide metabolites. These lipid metabolites originate from the epoxidation of ω-3 endocannabinoids, docosahexanoyl ethanolamide (DHEA) and eicosapentaenoyl ethanolamide (EPEA) by cytochrome P450 (CYP) epoxygenases to form epoxydocosapentaenoic acid-ethanolamides (EDP-EAs) and epoxyeicosatetraenoic acid-ethanolamides (EEQ-EAs), respectively. The EDP-EAs and EEQ-EAs are endogenously produced in rat brain and peripheral organs. Additionally, EDP-EAs and EEQ-EAs dose-dependently decrease pro-inflammatory IL-6 cytokine and increased anti-inflammatory IL-10 cytokine. Furthermore, the EEQ-EAs and EDP-EAs attenuate angiogenesis and cell migration in cancer cells, induce vasodilation in bovine coronary arteries, and reciprocally regulate platelet aggregation in washed human platelets. Taken together, the ω-3 endocannabinoid epoxides represent a new class of dual acting molecules that display unique pharmacological properties.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

2-AG:

2-arachidonoyl-glycerol

2-DHG:

2-docosahexaenoyl-glycerol

2-EPG:

2-eicosapentaenoyl-glycerol

AA:

arachidonic acid

AEA:

anandamide

cAMP:

cyclic adenosine monophosphate

CB1:

cannabinoid receptor 1

CB2:

cannabinoid receptor 2

CYP:

cytochrome P450

DHA:

docosahexaenoic acid

DHEA:

docosahexaenoyl ethanolamide

eCB:

endocannabinoid

EDP-EA:

docosapentaenoic acid ethanolamide

EEQ-EA:

epoxyeicosatetraenoic acid ethanolamide

EPA:

eicosapentaenoic acid

EPEA:

eicosapentaenoyl ethanolamide

FAAH:

fatty amide hydrolase

GPCR:

G-Protein coupled receptor

MAGL:

monoacylglycerol lipase

sEH:

soluble epoxide hydrolase

Δ9-THC:

Δ9-tetrahydrocannabinol

References

  1. Matsuda LA, Lolait SJ, Brownstein MJ et al (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564. https://doi.org/10.1038/346561a0

    Article  CAS  PubMed  Google Scholar 

  2. Devane WA, Dysarz FA, Johnson RM et al (1988) Determination rat brain and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 34:605–613

    CAS  PubMed  Google Scholar 

  3. Fride E (2002) Endocannabinoids in the central nervous system – an overview. Prostaglandins Leukot Essent Fat Acids 66:221–233. https://doi.org/10.1054/plef.2001.0360

    Article  CAS  Google Scholar 

  4. Bátkai S, Pacher P, Osei-Hyiaman D et al (2004) Endocannabinoids acting at cannabinoid-1 receptors regulate cardiovascular function in hypertension. Circulation 110:1996–2002. https://doi.org/10.1161/01.CIR.0000143230.23252.D2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Zelasko S, Arnold WR, Das A (2015) Endocannabinoid metabolism by cytochrome P450 monooxygenases. Prostaglandins Other Lipid Mediat 116–117:112–123. https://doi.org/10.1016/j.prostaglandins.2014.11.002

    Article  CAS  PubMed  Google Scholar 

  6. Galiegue S, Mary S, Marchand J et al (1995) Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem 232:54–61. https://doi.org/10.1111/j.1432-1033.1995.tb20780.x

    Article  CAS  PubMed  Google Scholar 

  7. Buckley NE, McCoy KL, Mezey É et al (2000) Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB2receptor. Eur J Pharmacol 396:141–149. https://doi.org/10.1016/S0014-2999(00)00211-9

    Article  CAS  PubMed  Google Scholar 

  8. Munro S, Thomas KL, Abu-Shaar M (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61–65. https://doi.org/10.1038/365061a0

    Article  CAS  PubMed  Google Scholar 

  9. Dhopeshwarkar A, Mackie K (2014) CB2 cannabinoid receptors as a therapeutic target–what does the future hold. Mol Pharmacol 86:430–437. https://doi.org/10.1124/mol.114.094649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Porter AC, Sauer J-MM, Knierman MD et al (2002) Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. J Pharmacol Exp Ther 301:1020–1024. https://doi.org/10.1124/jpet.301.3.1020

    Article  CAS  PubMed  Google Scholar 

  11. Pertwee RG (2006) Cannabinoid pharmacology: the first 66 years. Br J Pharmacol 147:S163. https://doi.org/10.1038/sj.bjp.0706406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Carnevale L, Arango A, Arnold WR et al (2018) Endocannabinoid virodhamine is an endogenous inhibitor of human cardiovascular CYP2J2 epoxygenase. Biochemistry 57:6489–6499. https://doi.org/10.1021/acs.biochem.8b00691

    Article  CAS  PubMed  Google Scholar 

  13. McDougle DR, Watson JE, Abdeen AA et al (2017) Anti-inflammatory ω-3 endocannabinoid epoxides. Proc Natl Acad Sci U S A 114:E6034–E6043. 201610325. https://doi.org/10.1073/pnas.1610325114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sagnella SM, Conn CE, Irena Krodkiewska XM, CJD (2011) Anandamide and analogous endocannabinoids: a lipid self-assembly study. Soft Matter 7:5319–5328. https://doi.org/10.1039/c1sm05141e

    Article  CAS  Google Scholar 

  15. Wood JT, Williams JS, Pandarinathan L et al (2010) Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma. J Lipid Res 51:1416–1423. https://doi.org/10.1194/jlr.M002436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sharir H, Console-Bram L, Mundy C et al (2012) The endocannabinoids anandamide and virodhamine modulate the activity of the candidate cannabinoid receptor GPR55. J Neuroimmune Pharmacol 7:856–865. https://doi.org/10.1007/s11481-012-9351-6

    Article  PubMed  PubMed Central  Google Scholar 

  17. Watanabe H, Vriens J, Prenen J et al (2003) Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature 424:434–438. https://doi.org/10.1038/nature01807

    Article  CAS  PubMed  Google Scholar 

  18. Cadas H, di Tomaso E, Piomelli D (1997) Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl phosphatidylethanolamine, in rat brain. J Neurosci 17:1226–1242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sun Y-X, Tsuboi K, Okamoto Y et al (2004) Biosynthesis of anandamide and N-palmitoylethanolamine by sequential actions of phospholipase A2 and lysophospholipase D. Biochem J 380:749–756. https://doi.org/10.1042/BJ20040031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Murataeva N, Straiker A, MacKie K (2014) Parsing the players: 2-arachidonoylglycerol synthesis and degradation in the CNS. Br J Pharmacol 171:1379–1391. https://doi.org/10.1111/bph.12411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cravatt BF, Lichtman AH (2003) Fatty acid amide hydrolase: an emerging therapeutic target in the endocannabinoid system. Curr Opin Chem Biol 7:469–475. https://doi.org/10.1016/S1367-5931(03)00079-6

    Article  CAS  PubMed  Google Scholar 

  22. Ahn K, Johnson DS, Cravatt BF (2010) NIH Public Access 4:763–784. https://doi.org/10.1517/17460440903018857.Fatty

  23. Labar G, Bauvois C, Borel F et al (2010) Crystal structure of the human monoacylglycerol lipase, a key actor in endocannabinoid signaling. Chembiochem 11:218–227. https://doi.org/10.1002/cbic.200900621

    Article  CAS  PubMed  Google Scholar 

  24. Kay A, Michele MK, Benjamin CF (2011) Enzymatic pathways that regulate endocannabinoid signaling in the nervous system. Chem Rev 108:1687–1707. https://doi.org/10.1021/cr0782067.Enzymatic

    Article  Google Scholar 

  25. Deutsch DG, Goligorsky MS, Schmid PC et al (1997) Production and physiological actions of anandamide in the vasculature of the rat kidney. J Clin Invest 100:1538–1546. https://doi.org/10.1172/JCI119677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Horne EA, Stella N (2008) The ins and outs of endocannabinoid signaling in healthy and diseased brain. Futur Lipidol 3:435–452. https://doi.org/10.2217/17460875.3.4.435

    Article  CAS  Google Scholar 

  27. Lu Y, Anderson HD (2017) Cannabinoid signaling in health and disease. Can J Physiol Pharmacol 95:311–327. https://doi.org/10.1139/cjpp-2016-0346

    Article  CAS  PubMed  Google Scholar 

  28. Chen S, Zhang H, Pu H et al (2014) Epoxy. Sci Rep 4:1–8. https://doi.org/10.1038/srep07458

    Article  CAS  Google Scholar 

  29. Mievis S, Blum D, Ledent C (2011) Worsening of Huntington disease phenotype in CB1 receptor knockout mice. Neurobiol Dis 42:524–529. https://doi.org/10.1016/j.nbd.2011.03.006

    Article  CAS  PubMed  Google Scholar 

  30. Ravinet Trillou C, Delgorge C, Menet C et al (2004) CB1 cannabinoid receptor knockout in mice leads to leanness, resistance to diet-induced obesity and enhanced leptin sensitivity. Int J Obes 28:640–648. https://doi.org/10.1038/sj.ijo.0802583

    Article  CAS  Google Scholar 

  31. Thomas F, Gamage AHL (2013) The endocannabinoid system: role in energy regulation. Trends Pharmacol Sci 58:144–148. https://doi.org/10.1002/pbc.23367.The

    Article  Google Scholar 

  32. Zimmer a M, Hohmann a G, Herkenham M, Bonner TI (1999) Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice. Proc Natl Acad Sci U S A 96:5780–5785. https://doi.org/10.1073/pnas.96.10.5780

    Article  PubMed  PubMed Central  Google Scholar 

  33. Benito C, Tolón RM, Pazos MR et al (2008) Cannabinoid CB 2 receptors in human brain inflammation. Br J Pharmacol 153:277–285. https://doi.org/10.1038/sj.bjp.0707505

    Article  CAS  PubMed  Google Scholar 

  34. Di Marzo V (2008) Targeting the endocannabinoid system: to enhance or reduce. Nat Rev Drug Discov 7:438–455. https://doi.org/10.1038/nrd2553

    Article  CAS  PubMed  Google Scholar 

  35. Di Marzo V, Stella N, Zimmer A (2014) Endocannabinoid signalling and the deteriorating brain. Nat Rev Neurosci 16:30–42. https://doi.org/10.1038/nrn3876

    Article  CAS  Google Scholar 

  36. Navarro G, Morales P, Rodríguez-Cueto C et al (2016) Targeting cannabinoid CB2receptors in the central nervous system. Medicinal chemistry approaches with focus on neurodegenerative disorders. Front Neurosci 10:1–11. https://doi.org/10.3389/fnins.2016.00406

    Article  Google Scholar 

  37. Zipp F, Aktas O (2006) The brain as a target of inflammation: common pathways link inflammatory and neurodegenerative diseases. Trends Neurosci 29:518–527. https://doi.org/10.1016/j.tins.2006.07.006

    Article  CAS  PubMed  Google Scholar 

  38. Kozak KR, Gupta RA, Moody JS et al (2002) 15-lipoxygenase metabolism of 2-arachidonylglycerol: generation of a peroxisome proliferator-activated receptor α agonist. J Biol Chem 277:23278–23286. https://doi.org/10.1074/jbc.M201084200

    Article  CAS  PubMed  Google Scholar 

  39. O’Sullivan SE (2007) Cannabinoids go nuclear: evidence for activation of peroxisome proliferator-activated receptors. Br J Pharmacol 152:576–582. https://doi.org/10.1038/sj.bjp.0707423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zygmunt PM, Petersson J, Andersson DA et al (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400:452–457

    Article  CAS  PubMed  Google Scholar 

  41. Rouzer CA, Marnett LJ (2011) Endocannabinoid oxygenation by cyclooxygenases, lipoxygenases, and cytochromes P450: cross-talk between the eicosanoid and endocannabinoid signaling pathways. Chem Rev 111:5899–5921. https://doi.org/10.1021/cr2002799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Yang R, Fredman G, Krishnamoorthy S et al (2011) Decoding functional metabolomics with docosahexaenoyl ethanolamide (DHEA) identifies novel bioactive signals∗. J Biol Chem 286:31532–31541. https://doi.org/10.1074/jbc.M111.237990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Aoki M, Matsumoto NM, Okubo Y, Ogawa R (2019) Bioelectrochemistry cytochrome P450 genes play central roles in transcriptional response by keratinocytes to a high-voltage alternating current electric fi eld. Bioelectrochemistry 126:163–171. https://doi.org/10.1016/j.bioelechem.2018.11.014

    Article  CAS  PubMed  Google Scholar 

  44. Snider NT, Nast JA, Tesmer LA, Hollenberg PF (2009) A cytochrome P450-derived epoxygenated metabolite of anandamide is a potent cannabinoid receptor 2-selective agonist. Mol Pharmacol 75:965–972. https://doi.org/10.1124/mol.108.053439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Snider NT, Walker VJ, Hollenberg PF (2010) Oxidation of the endogenous cannabinoid arachidonoyl ethanolamide by the cytochrome P450 monooxygenases: physiological and pharmacological implications. Pharmacol Rev 62:136–154. https://doi.org/10.1124/pr.109.001081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Walker VJ, Griffin AP, Hammar DK, Hollenberg PF (2016) Metabolism of anandamide by human cytochrome P450 2J2 in the reconstituted system and human intestinal microsomes. J Pharmacol Exp Ther 357:537–544. https://doi.org/10.1124/jpet.116.232553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kalish BT, Kieran MW, Puder M, Panigrahy D (2013) The growing role of eicosanoids in tissue regeneration, repair, and wound healing. Prostaglandins Other Lipid Mediat 104–105:130–138. https://doi.org/10.1016/j.prostaglandins.2013.05.002

    Article  CAS  PubMed  Google Scholar 

  48. Node K, Huo Y, Ruan X et al (1999) Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids. Science 285(80):1276–1279. https://doi.org/10.1126/science.285.5431.1276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Zhao H, Chen J, Chai J et al (2017) Cytochrome P450 (CYP) epoxygenases as potential targets in the management of impaired diabetic wound healing. Lab Investig 97:782–791. https://doi.org/10.1038/labinvest.2017.21

    Article  CAS  PubMed  Google Scholar 

  50. McDougle DR, Kambalyal A, Meling DD, Das A (2014) Endocannabinoids anandamide and 2-Arachidonoylglycerol are substrates for human CYP2J2 Epoxygenase. J Pharmacol Exp Ther 351:616–627. https://doi.org/10.1124/jpet.114.216598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Snider NT, Kornilov AM, Kent UM, Hollenberg PF (2007) Anandamide metabolism by human liver and kidney microsomal cytochrome p450 enzymes to form hydroxyeicosatetraenoic and epoxyeicosatrienoic acid ethanolamides. J Pharmacol Exp Ther 321:590–597. https://doi.org/10.1124/jpet.107.119321.hydrolysis

    Article  CAS  PubMed  Google Scholar 

  52. Meunier B, de Visser SP, Shaik S (2004) Mechanism of oxidation reactions catalyzed by cytochrome P450 enzymes. Chem Rev 104:3947–3980. https://doi.org/10.1021/cr020443g

    Article  CAS  PubMed  Google Scholar 

  53. Berger A, Crozier G, Bisogno T et al (2001) Anandamide and diet: inclusion of dietary arachidonate and docosahexaenoate leads to increased brain levels of the corresponding N-acylethanolamines in piglets. Proc Natl Acad Sci 98:6402–6406. https://doi.org/10.1073/pnas.101119098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Dennis M (2010) Inflammatory hyperalgesia induces essential bioactive lipid production in the spinal cord. J Neurochem 114:981–993

    PubMed  PubMed Central  Google Scholar 

  55. Bisogno T, Delton-Vandenbroucke I, Milone A, Lagarde MDMV (1999) Biosynthesis and inactivation of N-arachidonoylethanolamine (anandamide) and N-docosahexaenoylethanolamine in bovine retina. Arch Biochem Biophys 370:300–307

    Article  CAS  PubMed  Google Scholar 

  56. Meijerink J, Balvers M, Witkamp R (2013) N-acyl amines of docosahexaenoic acid and other n-3 polyunsatured fatty acids – from fishy endocannabinoids to potential leads. Br J Pharmacol 169:772–783. https://doi.org/10.1111/bph.12030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Cui X, Kawashima H, Barclay TB et al (2001) Molecular cloning and regulation of expression of two novel mouse CYP4F genes: expression in peroxisome proliferator-activated receptor alpha-deficient mice upon lipopolysaccharide and clofibrate challenges. J Pharmacol Exp Ther 296:542–550

    CAS  PubMed  Google Scholar 

  58. Maresz K, Carrier EJ, Ponomarev ED et al (2005) Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli. J Neurochem 95:437–445. https://doi.org/10.1111/j.1471-4159.2005.03380.x

    Article  CAS  PubMed  Google Scholar 

  59. Zhang G, Panigrahy D, Mahakian LM et al (2013) Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis. Proc Natl Acad Sci 110:6530–6535. https://doi.org/10.1073/pnas.1304321110

    Article  PubMed  PubMed Central  Google Scholar 

  60. Hanuš L, Gopher A, Almog S, Mechoulam R (1993) Two new unsaturated fatty acid ethanolamides in brain that bind to the cannabinoid receptor. J Med Chem 36:3032–3034. https://doi.org/10.1021/jm00072a026

    Article  PubMed  Google Scholar 

  61. Thomas BF, Adams IB, Mascarella SW et al (1996) Structure-activity analysis of anandamide analogs: relationship to a cannabinoid pharmacophore. J Med Chem 39:471–479. https://doi.org/10.1021/jm9505167

    Article  CAS  PubMed  Google Scholar 

  62. Morisseau C, Inceoglu B, Schmelzer K et al (2010) Naturally occurring monoepoxides of eicosapentaenoic acid and docosahexaenoic acid are bioactive antihyperalgesic lipids. J Lipid Res 51:3481–3490. https://doi.org/10.1194/jlr.M006007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Coussens LM, Werb Z (2002) Inflammation and cancer. Pharmaceut Biotechnol 420(6917)860. Nature 420:860–867. https://doi.org/10.1038/nature01322.Inflammation

  64. Jaudszus A, Gruen M, Watzl B et al (2013) Evaluation of suppressive and pro-resolving effects of EPA and DHA in human primary monocytes and T-helper cells. J Lipid Res 54:923–935. https://doi.org/10.1194/jlr.P031260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Laviano A, Rianda S, Molfino A, Fanelli FR (2013) Omega-3 fatty acids in cancer. Curr Opin Clin Nutr Metab Care 16:156–161. https://doi.org/10.1097/MCO.0b013e32835d2d99

    Article  CAS  PubMed  Google Scholar 

  66. Cui PH, Petrovic N, Murray M (2011) The ω-3 epoxide of eicosapentaenoic acid inhibits endothelial cell proliferation by p38 MAP kinase activation and cyclin D1/CDK4 down-regulation. Br J Pharmacol 162:1143–1155. https://doi.org/10.1111/j.1476-5381.2010.01113.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Guodong Z, Dipak P, Lisa MM et al (2013) Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis. Proc Natl Acad Sci 110:6530–6535. https://doi.org/10.1073/pnas.1304321110/-/DCSupplemental. www.pnas.org/cgi/doi/10.1073/pnas.1304321110

    Article  Google Scholar 

  68. Roy J, Watson JE, Hong IS et al (2018) Antitumorigenic properties of omega-3 endocannabinoid epoxides. J Med Chem 61:5569–5579. https://doi.org/10.1021/acs.jmedchem.8b00243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Hammock BD, Wagner Karen IB (2011) The soluble epoxide hydrolase as a pharmaceutical target for pain management. Pain Manag 50:383–386. https://doi.org/10.1097/FJC.0b013e3181506445

    Article  CAS  Google Scholar 

  70. Sasso O, Wagner K, Morisseau C et al (2015) Peripheral FAAH and soluble epoxide hydrolase inhibitors are synergistically antinociceptive. Pharmacol Res 97:7–15. https://doi.org/10.1016/j.phrs.2015.04.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Chen JK, Chen JK, Imig JD et al (2008) Identification of novel endogenous cytochrome P450 arachidonate metabolites with high affinity for cannabinoid receptors. J Biol Chem 283:24514–24524. https://doi.org/10.1074/jbc.M709873200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Bisogno T, Melck D, Bobrov M et al (2000) N-acyl-dopamines: novel synthetic CB1 cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo. Biochem J 351:817. https://doi.org/10.1042/bj3510817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Fowler CJ, Tiger G, López-Rodríguez ML et al (2003) Inhibition of fatty acid amidohydrolase, the enzyme responsible for the metabolism of the endocannabinoid anandamide, by analogues of arachidonoyl-serotonin. J Enzyme Inhib Med Chem 18:225–231. https://doi.org/10.1080/1475636031000080216

    Article  CAS  PubMed  Google Scholar 

  74. Wang Y, Balvers MGJ, Hendriks HFJ et al (2017) Docosahexaenoyl serotonin emerges as most potent inhibitor of IL-17 and CCL-20 released by blood mononuclear cells from a series of N-acyl serotonins identified in human intestinal tissue. Biochim Biophys Acta Mol Cell Biol Lipids 1862:823–831. https://doi.org/10.1016/j.bbalip.2017.05.008

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was partly supported by American Heart Association Scientist Development Grant 15SDG25760064 (A.D.), National Institutes of Health (NIH) Grant R01 GM1155884 (A.D.), and R03 DA042365 (A.D). We would like to acknowledge Daniel R. McDougle, William R. Arnold, Jahnabi Roy, and Josephine E. Watson for doing the research related to omega-3 endocannabinoid epoxides.

Conflict of Interest Statement

The authors declare no competing financial interest.

Author information

Authors and Affiliations

  1. Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL, USA

    Lauren N. Carnevale & Aditi Das

  2. Department of Comparative Biosciences, University of Illinois Urbana-Champaign, Urbana, IL, USA

    Aditi Das

  3. Center for Biophysics and Quantitative Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA

    Aditi Das

  4. Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL, USA

    Aditi Das

  5. Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL, USA

    Aditi Das

  6. Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA

    Aditi Das

Authors
  1. Lauren N. Carnevale
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aditi Das
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aditi Das .

Editor information

Editors and Affiliations

  1. 431 Chemistry Building, Wayne State University, Detroit, MI, USA

    Kenneth V. Honn

  2. National Institutes of Health, Durham, NC, USA

    Darryl C. Zeldin

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Carnevale, L.N., Das, A. (2019). Novel Anti-inflammatory and Vasodilatory ω-3 Endocannabinoid Epoxide Regioisomers. In: Honn, K., Zeldin, D. (eds) The Role of Bioactive Lipids in Cancer, Inflammation and Related Diseases. Advances in Experimental Medicine and Biology, vol 1161. Springer, Cham. https://doi.org/10.1007/978-3-030-21735-8_17

Download citation

Publish with us

Policies and ethics

Search

Navigation