Elsevier

Pharmacological Research

Volume 42, Issue 4, October 2000, Pages 317-322
Pharmacological Research

Regular Article
2-arachidonyl-glycerol stimulates nitric oxide release from human immune and vascular tissues and invertebrate immunocytes by cannabinoid receptor 1

https://doi.org/10.1006/phrs.2000.0702Get rights and content

Abstract

The pharmacological physiological effects of the endogenous cannabinomimetic (endocannabinoid) anandamide have been well characterized. Another endocannabinoid, 2-arachidonoyl-glycerol (2-AG), has been less-widely studied. 2-AG occurs in vertebrate and invertebrate tissues and binds to both cannabinoid receptors (CB1 and CB2). In the current study, 2-AG was found to cause human monocytes and immunocytes from Mytilus edulis to become round and immobile, which may correlate with decreased production of cytokines and adhesion molecules, i.e. an immunosuppressive response. In addition, exposure of these cells to 2-AG results in nitric oxide (NO) release, which is blocked by the nitric oxide synthase inhibitor, l-NAME and a CB1 antagonist, but not by a CB2 antagonist. The results obtained in the human vascular system were similar to those obtained in immune cells. Treatment of human saphenous veins and atria with 2-AG stimulated basal NO release, which was antagonized by l-NAME and a CB1 antagonist. Taken together these results indicate that 2-AG exerts immune and vascular actions similar to those observed with anandamide.

References (47)

  • T Sugiura et al.

    Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor–Structure-activity relationship of 2-arachidonoylglycerolether-linked analogues, and related compounds

    J Biol Chem

    (1999)
  • JC Schon et al.

    Microscopic computer-assisted analysis of conformational state: Reference to neuroimmunology

    Adv Neuroimmunol

    (1991)
  • MA Shipp et al.

    CD10 (CALLA)/neutral endopeptidase 24.11 modulates inflammatory peptide-induced changes in neutrophil morphology, migration, and adhesion proteins and is itself regulated by neutrophil activation

    Blood

    (1991)
  • GB Stefano et al.

    Presence of the mu3 opiate receptor in endothelial cells: Coupling to nitric oxide production and vasodilation

    J Biol Chem

    (1995)
  • GB Stefano et al.

    Macrophage behavior associated with acute and chronic exposure to HIV GP120, morphine and anandamide: Endothelial implications

    Int J Cardiol

    (1998)
  • GA Cabral et al.

    Inhibition of macrophage inducible protein expression by delta-9-tetrahydrocannabinol

    Life Sci

    (1994)
  • GB Stefano

    Autoimmunovascular regulation: Morphine and anandamide stimulated nitric oxide release

    J Neuroimmunol

    (1998)
  • C Fimiani et al.

    Morphine and anandamide stimulate intracellular calcium transients in human arterial endothelial cells: Coupling to nitric oxide release

    Cell Signal

    (1999)
  • WA Devane et al.

    Isolation and structure of a brain constituent that binds to the cannabinoid receptor

    Science

    (1992)
  • V DiMarzo et al.

    Biochemistry of the endogenous ligands of cannabinoid receptors

    Sem. Neurosci. (in press)

    (1998)
  • H Schuel et al.

    Anandamide (arachidonylethanolamide), a brain cannabinoid receptor agonist, reduces sperm fertilizing capacity in sea urchins by inhibiting the acrosome reaction

    Proc Natl Acad Sci, USA

    (1994)
  • T Bisogno et al.

    Release and degradation of the novel endogenous cannabimimetic metabolite 2-Arachidonoylglycerol in mouse neuroblastoma cells

    Biochem J

    (1997)
  • N Stella et al.

    A second endogenous cannabinoid that modulates long-term potentiation

    Nature

    (1997)
  • Cited by (0)

    1

    Corresponding author. E-mail: [email protected] or [email protected]

    View full text