Opposite control of frontocortical 2-arachidonoylglycerol turnover rate by cannabinoid type-1 receptors located on glutamatergic neurons and on astrocytes.
J. Neurochem.. 2015-02-25; 133(1): 26-37
DOI: 10.1111/jnc.13044
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1. J Neurochem. 2015 Apr;133(1):26-37. doi: 10.1111/jnc.13044. Epub 2015 Feb 25.
Opposite control of frontocortical 2-arachidonoylglycerol turnover rate by
cannabinoid type-1 receptors located on glutamatergic neurons and on astrocytes.
Belluomo I(1), Matias I, Pernègre C, Marsicano G, Chaouloff F.
Author information:
(1)Plateforme de Chimie Analytique, NeuroCentre INSERM U862, Bordeaux, France.
This study examined the respective influences of cannabinoid type-1 (CB1)
receptors expressed either in forebrain GABAergic neurons, in cortical
glutamatergic neurons, or in astrocytes on the turnover rates of the
endocannabinoids N-arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol
(2-AG), and the non-cannabinoid N-acylethanolamides, palmitoylethanolamide (PEA),
and oleoylethanolamide (OEA), in mouse forebrain regions. To this end,
conditional mutant mice lacking CB1 receptors from either of these cell types
were pre-treated systemically with JZL195, a dual inhibitor of fatty acid amide
hydrolase, the enzyme degrading AEA, PEA, and OEA, and of monoacylglycerol
lipase, the main 2-AG-degrading enzyme. The analyses of frontocortical,
hippocampal, and striatal AEA, 2-AG, PEA, and OEA concentrations revealed that
their respective baseline concentrations were not influenced by the mouse
genotype. On the other hand, the accumulation of frontocortical and/or
hippocampal 2-AG levels in JZL195-pre-treated mice was dependent on the mouse
genotype. Thus, JZL195-induced 2-AG accumulation rates were diminished in the
frontal cortex of mice lacking CB1 receptors in glutamatergic neurons while their
respective values were increased in the frontal cortex and hippocampus of mice
lacking these receptors in astrocytes. These genotypic differences occurred with
parallel and proportionate changes in the fractional rate constants for
degradation of 2-AG, thus providing a mechanism whereby the baseline levels of
2-AG remained constant between genotypes. Besides suggesting a cell-type-specific
control of frontocortical and/or hippocampal 2-AG synthesis and degradation rates
by CB1 receptors, this study highlights the interest of assessing endocannabinoid
turnover rates when questioning the status of the endocannabinoid system.
© 2015 International Society for Neurochemistry.
DOI: 10.1111/jnc.13044
PMID: 25626460 [Indexed for MEDLINE]