A role for monoglyceride lipase in 2-arachidonoylglycerol inactivation

Thien P. Dinh, T. Freund, Daniele Piomelli

Research output: Contribution to journalArticle

230 Citations (Scopus)

Abstract

2-Arachidonoylglycerol (2-AG) is a naturally occurring monoglyceride that activates cannabinoid receptors and meets several key requisites of an endogenous cannabinoid substance. It is present in the brain (where its levels are 170-folds higher than those of anandamide), is produced by neurons in an activity- and calcium-dependent manner, and is rapidly eliminated. The mechanism of 2-AG inactivation is not completely understood, but is thought to involve carrier-mediated transport into cells followed by enzymatic hydrolysis. We examined the possible role of the serine hydrolase, monoglyceride lipase (MGL), in brain 2-AG inactivation. We identified by homology screening a cDNA sequence encoding for a 303-amino acid protein, which conferred MGL activity upon transfection to COS-7 cells. Northern blot and in situ hybridization analyses revealed that MGL mRNA is unevenly present in the rat brain, with highest levels in regions where CB1 cannabinoid receptors are also expressed (hippocampus, cortex, anterior thalamus and cerebellum). Immunohistochemical studies in the hippocampus showed that MGL distribution has striking laminar specificity, suggesting a presynaptic localization of the enzyme. Adenovirus-mediated transfer of MGL cDNA into rat cortical neurons increased the degradation of endogenously produced 2-AG in these cells, whereas no such effect was observed on anandamide degradation. These results indicate that hydrolysis via MGL may be a primary route of 2-AG inactivation in intact neuronal cells.

Original languageEnglish
Pages (from-to)149-158
Number of pages10
JournalChemistry and Physics of Lipids
Volume121
Issue number1-2
DOIs
Publication statusPublished - Dec 31 2002

Fingerprint

Monoacylglycerol Lipases
Brain
Neurons
Rats
Hippocampus
Hydrolysis
Complementary DNA
Anterior Thalamic Nuclei
Monoglycerides
Hydrolases
Cannabinoid Receptor CB1
Degradation
Cannabinoid Receptors
Enzymatic hydrolysis
Carrier transport
Cannabinoids
COS Cells
Adenoviridae
Northern Blotting
Cerebellum

Keywords

  • 2-Arachidonoylglycerol
  • Anandamide
  • Endocannabinoids
  • Fatty acid amide hydrolase
  • Monoglyceride lipase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics

Cite this

A role for monoglyceride lipase in 2-arachidonoylglycerol inactivation. / Dinh, Thien P.; Freund, T.; Piomelli, Daniele.

In: Chemistry and Physics of Lipids, Vol. 121, No. 1-2, 31.12.2002, p. 149-158.

Research output: Contribution to journalArticle

Dinh, Thien P. ; Freund, T. ; Piomelli, Daniele. / A role for monoglyceride lipase in 2-arachidonoylglycerol inactivation. In: Chemistry and Physics of Lipids. 2002 ; Vol. 121, No. 1-2. pp. 149-158.
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