2-Arachidonoylglycerol, a putative endogenous cannabinoid receptor ligand, induces rapid, transient elevation of intracellular free Ca2+ in neuroblastoma x glioma hybrid NG108-15 cells

Biochem Biophys Res Commun. 1996 Dec 4;229(1):58-64. doi: 10.1006/bbrc.1996.1757.

Abstract

Low concentrations of 2-arachidonoylglycerol were found to induce rapid, transient elevation of intracellular free Ca2+ in NG108-15 cells (EC50 was 150 nM). Free arachidonic acid, 2-palmitoylglycerol, 2-oleoylglycerol, 2-linoleoylglycerol and 2-docosahexaenoylglycerol were inactive. Anandamide acted as a partial agonist. Importantly, desensitization was observed upon sequential challenge with 2-arachidonoylglycerol. Furthermore, cross-desensitization was observed between 2-arachidonoylglycerol and WIN 55212-2, a cannabinoid receptor agonist. Pretreatment of the cells with SR141716A, a cannabinoid receptor antagonist, abolished the activities of both 2-arachidonoylglycerol and WIN 55212-2. These results strongly suggest that 2-arachidonoylglycerol and WIN 55212-2 bind to a common cannabinoid receptor to elicit cellular responses and that 2-arachidonoylglycerol has some physiological role in nervous tissues.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonic Acids / pharmacology
  • Benzoxazines
  • Calcium / metabolism*
  • Cannabinoids / metabolism
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Endocannabinoids
  • Glioma
  • Glycerides / chemistry
  • Glycerides / pharmacology*
  • Hybrid Cells
  • Ligands
  • Morpholines / pharmacology
  • Naphthalenes / pharmacology
  • Neuroblastoma
  • Neurons / drug effects*
  • Piperidines / pharmacology
  • Platelet Activating Factor / pharmacology
  • Polyunsaturated Alkamides
  • Pyrazoles / pharmacology
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists
  • Receptors, Drug / antagonists & inhibitors
  • Receptors, Drug / metabolism*
  • Rimonabant

Substances

  • Arachidonic Acids
  • Benzoxazines
  • Cannabinoids
  • Endocannabinoids
  • Glycerides
  • Ligands
  • Morpholines
  • Naphthalenes
  • Piperidines
  • Platelet Activating Factor
  • Polyunsaturated Alkamides
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • glyceryl 2-arachidonate
  • Rimonabant
  • Calcium
  • anandamide