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    Last Name

    Sumner H Burstein PhD

    TitleProfessor Emeritus
    InstitutionUniversity of Massachusetts Medical School
    DepartmentBiochemistry and Molecular Pharmacology
    AddressUniversity of Massachusetts Medical School
    364 Plantation Street, LRB
    Worcester MA 01605

        Academic History

        Photo: Sumner Burstein, PhD BS, Massachusetts Institute of Technology, 1953
        PhD, Wayne State University, 1959
        Postdoctoral Training
        Fellow, Weizmann Institute, 1960
        Fellow, Brandeis University, 1961

        Lipid Mediated Signaling Pathways

                 My current research interest is in the area of bioactive lipid-mediated signaling pathways. N-arachidonoyl glycine (NAGly), an endogenous lipoamino acid, with potential physiological and pharmacological significance, is found at high levels in rat brain, spinal cord and other sites throughout the body. It is the simplest member of a subfamily of the super family of eicosanoids, and comprises more than 50 members.  Prior reports had shown that NAGly acts to elicit analgesic properties similar to those reported for the closely related endocannabinoid anandamide. It is a putative ligand for GPR18, a GPCR expressed in spleen, testis and brain where it plays a role in induced cellular migration of cells to sites of damage. Unlike anandamide, NAGly does not bind to either the CB1 or CB2 cannabinoid receptors, and thus exhibits no psychotropic activity. NAGly also displays modest activity as an in vitro inhibitor of FAAH, the enzyme primarily responsible for the inactivation of anandamide under physiological conditions. We do not believe this effect results in anti-inflammatory action. However, NAGly binds with high affinity to GPR18 resulting in a robust increase of the anti-inflammatory eicosanoid PGJ. A growing body of reports indicates a wide range of functional responses for NAGly, however, none address the subject of receptor-mediated signaling pathways. An understanding of the pathways would open the way for the discovery of potent analogs of NAgly that would be candidates for therapeutic agents, which is my long-term goal.

         A Novel Bioactive Lipid Mediated Signaling Pathway

        A novel bioactive lipid signaling pathway

        Putative mechanisms for analgesic and anti-inflammatory actions of NAgly.

         1. Inhibition of FAAH elevates anandamide and 2-AG levels (Burstein et al., 2002; Cascio et al., 2004; Huang et al., 2001).

        2. Anandamide activates CB1 and CB2 (Axelrod et al., 1998; Barnett-Norris et al., 1998).

        3. Receptor activation produces analgesia (Stein et al., 1996; Walker et al., 1999).

        4. NAgly binds to PPAR-g (Burstein, 2005).

        5. PPAR-g elevates COX-2 expression (Na et al., 2003).

        6. COX-2 mediates PGD2 synthesis (Na et al., 2003).

        7. Unregulated transformation to PGJ products (Na et al., 2003).

        8. PGJ2 promotes resolution of chronic inflammation (Gilroy et al., 1999).

        9. Possible positive feedback to PPAR-g  (Farnesi-de-Assuncao et al., 2012)

        10. NAgly binds to GPR-18 (Burstein et al.,unpublished).

        11. Inhibition of forskolin-stimulated adenylate cyclase (Kohno et al., 2006).

        12. Activation of phospholipases (Exton, 1996).

        13. Release of free arachidonic acid (Burstein et al.,unpublished).

        14. Increased lipoxin A4 and PGJ2 synthesis (Burstein et al.,unpublished).

        15. Lipoxin A4 promotes resolution of chronic inflammation (Serhan, 2007).


        selected publications
        List All   |   Timeline
        1. Burstein S. Cannabidiol (CBD) and its analogs: a review of their effects on inflammation. Bioorg Med Chem. 2015 Apr 1; 23(7):1377-85.
          View in: PubMed
        2. Tepper MA, Zurier RB, Burstein SH. Ultrapure ajulemic acid has improved CB2 selectivity with reduced CB1 activity. Bioorg Med Chem. 2014 Jul 1; 22(13):3245-51.
          View in: PubMed
        3. Burstein SH. The cannabinoid acids, analogs and endogenous counterparts. Bioorg Med Chem. 2014 May 15; 22(10):2830-43.
          View in: PubMed
        4. Burstein SH, Tepper MA. In vitro metabolism and metabolic effects of ajulemic acid, a synthetic cannabinoid agonist. Pharmacol Res Perspect. 2013 Dec; 1(2):e00017.
          View in: PubMed
        5. Kattamuri PV, Salmonsen R, McQuain C, Burstein S, Sun H, Li G. Asymmetric synthesis of novel N-(1-phenyl-2,3-dihydroxypropyl)arachidonylamides and evaluation of their anti-inflammatory activity. Life Sci. 2013 Mar 19; 92(8-9):506-11.
          View in: PubMed
        6. Burstein S, McQuain C, Salmonsen R, Seicol B. N-Amino acid linoleoyl conjugates: anti-inflammatory activities. Bioorg Med Chem Lett. 2012 Jan 15; 22(2):872-5.
          View in: PubMed
        7. Burstein SH, McQuain CA, Ross AH, Salmonsen RA, Zurier RE. Resolution of inflammation by N-arachidonoylglycine. J Cell Biochem. 2011 Nov; 112(11):3227-33.
          View in: PubMed
        8. Tan B, O'Dell DK, Yu YW, Monn MF, Hughes HV, Burstein S, Walker JM. Identification of endogenous acyl amino acids based on a targeted lipidomics approach. J Lipid Res. 2010 Jan; 51(1):112-9.
          View in: PubMed
        9. Burstein SH, Zurier RB. Cannabinoids, endocannabinoids, and related analogs in inflammation. AAPS J. 2009 Mar; 11(1):109-19.
          View in: PubMed
        10. Bradshaw HB, Rimmerman N, Hu SS, Burstein S, Walker JM. Novel endogenous N-acyl glycines identification and characterization. Vitam Horm. 2009; 81:191-205.
          View in: PubMed
        11. Burstein S, Salmonsen R. Acylamido analogs of endocannabinoids selectively inhibit cancer cell proliferation. Bioorg Med Chem. 2008 Nov 15; 16(22):9644-51.
          View in: PubMed
        12. Stebulis JA, Johnson DR, Rossetti RG, Burstein SH, Zurier RB. Ajulemic acid, a synthetic cannabinoid acid, induces an antiinflammatory profile of eicosanoids in human synovial cells. Life Sci. 2008 Nov 7; 83(19-20):666-70.
          View in: PubMed
        13. Rimmerman N, Bradshaw HB, Hughes HV, Chen JS, Hu SS, McHugh D, Vefring E, Jahnsen JA, Thompson EL, Masuda K, Cravatt BF, Burstein S, Vasko MR, Prieto AL, O'Dell DK, Walker JM. N-palmitoyl glycine, a novel endogenous lipid that acts as a modulator of calcium influx and nitric oxide production in sensory neurons. Mol Pharmacol. 2008 Jul; 74(1):213-24.
          View in: PubMed
        14. Burstein S. The elmiric acids: biologically active anandamide analogs. Neuropharmacology. 2008 Dec; 55(8):1259-64.
          View in: PubMed
        15. Ambrosio AL, Dias SM, Polikarpov I, Zurier RB, Burstein SH, Garratt RC. Ajulemic acid, a synthetic nonpsychoactive cannabinoid acid, bound to the ligand binding domain of the human peroxisome proliferator-activated receptor gamma. J Biol Chem. 2007 Jun 22; 282(25):18625-33.
          View in: PubMed
        16. Burstein SH, Adams JK, Bradshaw HB, Fraioli C, Rossetti RG, Salmonsen RA, Shaw JW, Walker JM, Zipkin RE, Zurier RB. Potential anti-inflammatory actions of the elmiric (lipoamino) acids. Bioorg Med Chem. 2007 May 15; 15(10):3345-55.
          View in: PubMed
        17. Johnson DR, Stebulis JA, Rossetti RG, Burstein SH, Zurier RB. Suppression of fibroblast metalloproteinases by ajulemic acid, a nonpsychoactive cannabinoid acid. J Cell Biochem. 2007 Jan 1; 100(1):184-90.
          View in: PubMed
        18. Burstein S. PPAR-gamma: a nuclear receptor with affinity for cannabinoids. Life Sci. 2005 Aug 19; 77(14):1674-84.
          View in: PubMed
        19. Burstein S. Ajulemic acid (IP-751): synthesis, proof of principle, toxicity studies, and clinical trials. AAPS J. 2005; 7(1):E143-8.
          View in: PubMed
        20. Salim K, Schneider U, Burstein S, Hoy L, Karst M. Pain measurements and side effect profile of the novel cannabinoid ajulemic acid. Neuropharmacology. 2005 Jun; 48(8):1164-71.
          View in: PubMed
        21. Burstein S, Zurier RB. Pain reduction and lack of psychotropic effects with ajulemic acid: comment on the article by Sumariwalla et al. Arthritis Rheum. 2004 Dec; 50(12):4078-9; author reply 4079-80.
          View in: PubMed
        22. Burstein SH, Karst M, Schneider U, Zurier RB. Ajulemic acid: A novel cannabinoid produces analgesia without a "high". Life Sci. 2004 Aug 6; 75(12):1513-22.
          View in: PubMed
        23. Grazia Cascio M, Minassi A, Ligresti A, Appendino G, Burstein S, Di Marzo V. A structure-activity relationship study on N-arachidonoyl-amino acids as possible endogenous inhibitors of fatty acid amide hydrolase. Biochem Biophys Res Commun. 2004 Jan 30; 314(1):192-6.
          View in: PubMed
        24. Karst M, Salim K, Burstein S, Conrad I, Hoy L, Schneider U. Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial. JAMA. 2003 Oct 1; 290(13):1757-62.
          View in: PubMed
        25. Bidinger B, Torres R, Rossetti RG, Brown L, Beltre R, Burstein S, Lian JB, Stein GS, Zurier RB. Ajulemic acid, a nonpsychoactive cannabinoid acid, induces apoptosis in human T lymphocytes. Clin Immunol. 2003 Aug; 108(2):95-102.
          View in: PubMed
        26. Liu J, Li H, Burstein SH, Zurier RB, Chen JD. Activation and binding of peroxisome proliferator-activated receptor gamma by synthetic cannabinoid ajulemic acid. Mol Pharmacol. 2003 May; 63(5):983-92.
          View in: PubMed
        27. Zurier RB, Rossetti RG, Burstein SH, Bidinger B. Suppression of human monocyte interleukin-1beta production by ajulemic acid, a nonpsychoactive cannabinoid. Biochem Pharmacol. 2003 Feb 15; 65(4):649-55.
          View in: PubMed
        28. Burstein SH, Huang SM, Petros TJ, Rossetti RG, Walker JM, Zurier RB. Regulation of anandamide tissue levels by N-arachidonylglycine. Biochem Pharmacol. 2002 Oct 1; 64(7):1147-50.
          View in: PubMed
        29. Burstein SH. Ajulemic acid (CT3): a potent analog of the acid metabolites of THC. Curr Pharm Des. 2000 Sep; 6(13):1339-45.
          View in: PubMed
        30. Burstein SH, Rossetti RG, Yagen B, Zurier RB. Oxidative metabolism of anandamide. Prostaglandins Other Lipid Mediat. 2000 Apr; 61(1-2):29-41.
          View in: PubMed
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