Elsevier

Life Sciences

Volume 65, Issues 6–7, 9 July 1999, Pages 645-655
Life Sciences

Biosynthesis and inactivation of endocannabinoids: Relevance to their proposed role as neuromodulators

https://doi.org/10.1016/S0024-3205(99)00287-8Get rights and content

Abstract

The two putative endogenous ligands of cannabinoid receptors, anandamide and 2-arachidonoylglycerol, are synthesized by and released from neurons in a Ca2+-dependent fashion, and re-uptaken and catabolized by both neurons and astrocytes. These biochemical features of the endocannabinoids, as well as some of their pharmacological effects in both central and peripheral nervous systems, suggest a role as neuromodulators for these metabolites. This neuromodulatory role is supported by the brain regional distribution of anandamide, its biosynthetic precursor and its major inactivating enzyme, and by the existence of possible regulatory mechanisms for the biosynthesis and inactivation of endocannabinoids, which are reviewed in this article.

References (82)

  • C.S. Breivogel et al.

    Neurobiol. Dis.

    (1998)
  • R.G. Pertwee

    Pharmacol. Ther.

    (1997)
  • V. Di Marzo et al.

    Trends Neurosci

    (1998)
  • V. Di Marzo et al.

    Prostaglandins Leukotrienes Essent. Fatty Acids

    (1995)
  • R. Mechoulam et al.

    Biochem. Pharmacol.

    (1995)
  • T. Sugiura et al.

    Biochem. Biophys. Res. Comm.

    (1995)
  • V. Di Marzo

    Biochim. Biophys. Acta

    (1998)
  • C.S. Breivogel et al.

    J. Biol. Chem.

    (1998)
  • H.H.O Schmid et al.

    Chem. Phys. Lipids

    (1996)
  • H.S. Hansen et al.

    Biochem. Pharmacol.

    (1998)
  • C.J. Hillard et al.

    J. Lipid Res.

    (1997)
  • K. Kempe et al.

    J. Biol. Chem.

    (1996)
  • C.C. Felder et al.

    FEBS Letts.

    (1996)
  • P.C. Schmid et al.

    FEBS Letts.

    (1995)
    P.C. Schmid et al.

    FEBS Letts.

    (1996)
  • D. Koga et al.

    J. Chromatogr.

    (1997)
  • T. Bisogno et al.

    Biochem. Biophys. Res. Commun.

    (1999)
  • T. Bisogno et al.

    Eur. J. Biochem.

    (1998)
  • M. Lagarde et al.

    Biochem. J.

    (1989)
  • D.G. Deutsch et al.

    Biochem. Pharmacol.

    (1993)
  • K.K. Kruszka et al.

    J. Biol. Chem.

    (1994)
  • W.A. Devane et al.
  • N. Ueda et al.

    J. Biol. Chem.

    (1995)
  • Y. Kurahashi et al.

    Biochem. Biophys. Res. Commun.

    (1997)
  • G. Arreaza et al.

    Neurosci. Lett.

    (1997)
  • V. Di Marzo et al.

    Nature

    (1994)
  • T. Sugiura et al.

    Eur. J. Biochem.

    (1996)
  • H. Cadas et al.

    J. Neurosci.

    (1997)
  • C.M. Gammon et al.

    J. Neurochem.

    (1989)
  • H.S. Hansen et al.

    J. Neurochem.

    (1997)
  • M. Maccarrone et al.

    J. Biol. Chem.

    (1998)
  • S. Ben-Shabat et al.

    Eur. J. Pharmacol.

    (1998)
  • V. Di Marzo et al.

    Biochem. J.

    (1998)
  • M. Egertova et al.
  • S.K. Goparaju et al.

    FEBS Lett.

    (1998)
  • K. Katayama et al.

    Biochim. Biophys. Acta

    (1997)
  • S.K. Goparaju et al.

    Biochem. Pharmacol.

    (1999)
  • W.S. Edgemond et al.

    Mol. Pharmacol.

    (1998)
  • R. Mechoulam et al.

    Nature

    (1997)
  • W.A. Devane et al.

    Science

    (1992)
  • C.C. Felder et al.

    J. Pharmacol. Exper. Ther.

    (1998)
  • E. Shohami et al.

    CNS Drug Rev.

    (1997)
  • Cited by (0)

    Fax: +39-081-8041770.

    View full text