Endocannabinoid metabolism in human glioblastomas and meningiomas compared to human non-tumour brain tissue.
The endogenous levels of the two cannabinoid receptor ligands 2-arachidonoyl glycerol and anandamide, and their respective congeners, monoacyl glycerols and N-acylethanolamines, as well as the phospholipid precursors of N-acylethanolamines, were measured by gas chromatography-mass spectrometry in glioblastoma (WHO grade IV) tissue and meningioma (WHO grade I) tissue and compared with human non-tumour brain tissue. Furthermore, the metabolic turnover of N-acylethanolamines was compared by measurements of the enzymatic activity of N-acyltransferase, N-acylphosphatidylethanolamine-hydrolysing phospholipase D and fatty acid amide hydrolase in the same three types of tissue. Glioblastomas were characterized by enhanced levels of N-acylethanolamines (eightfold, 128 +/- 59 pmol/micromol lipid phosphorus) including anandamide (17-fold, 4.6 +/- 3.1 pmol/micromol lipid phosphorus) and several species of N-acylphosphatidylethanolamines (three to eightfold). This was accompanied by a more than 60% reduction in the enzyme activities of N-acylphosphatidylethanolamine-hydrolysing phospholipase D and fatty acid amide hydrolase. By contrast, meningiomas were characterized by a massively enhanced level of 2-monoacyl glycerols (20-fold, 2293 +/- 361 pmol/micromol lipid phosphorus) including 2-arachidonoyl glycerol (20-fold, 1524 +/- 361 pmol/micromol lipid phosphorus). This was accompanied by an enhanced in vitro conversion of phosphatidylcholine to monoacyl glycerol (fivefold). The enhanced level of the 2-arachidonoyl glycerol, anandamide and other N-acylethanolamines detected in the two types of tumour tissue may possibly act as endogenous anti-tumour mediators by stimulation of both cannabinoid and non-cannabinoid receptor-mediated mechanisms.
Petersen
Gitte
G
Department of Pharmacology, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark.
Moesgaard
Birthe
B
Schmid
Patricia C
PC
Schmid
Harald H O
HH
Broholm
Helle
H
Kosteljanetz
Michael
M
Hansen
Harald S
HS
D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D063388:Endocannabinoids; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008579:Meningioma / Q000378:metabolism* / Q000473:pathology
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids