Philip Kingsley
Last active: 3/12/2020

Detection of Cyclooxygenase-2-Derived Oxygenation Products of the Endogenous Cannabinoid 2-Arachidonoylglycerol in Mouse Brain.

Morgan AJ, Kingsley PJ, Mitchener MM, Altemus M, Patrick TA, Gaulden AD, Marnett LJ, Patel S
ACS Chem Neurosci. 2018 9 (7): 1552-1559

PMID: 29722963 · PMCID: PMC6081739 · DOI:10.1021/acschemneuro.7b00499

Cyclooxygenase-2 (COX-2) catalyzes the formation of prostaglandins, which are involved in immune regulation, vascular function, and synaptic signaling. COX-2 also inactivates the endogenous cannabinoid (eCB) 2-arachidonoylglycerol (2-AG) via oxygenation of its arachidonic acid backbone to form a variety of prostaglandin glyceryl esters (PG-Gs). Although this oxygenation reaction is readily observed in vitro and in intact cells, detection of COX-2-derived 2-AG oxygenation products has not been previously reported in neuronal tissue. Here we show that 2-AG is metabolized in the brain of transgenic COX-2-overexpressing mice and mice treated with lipopolysaccharide to form multiple species of PG-Gs that are detectable only when monoacylglycerol lipase is concomitantly blocked. Formation of these PG-Gs is prevented by acute pharmacological inhibition of COX-2. These data provide evidence that neuronal COX-2 is capable of oxygenating 2-AG to form a variety PG-Gs in vivo and support further investigation of the physiological functions of PG-Gs.

MeSH Terms (18)

Animals Arachidonic Acids Brain Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Endocannabinoids Esters Female Glycerides Inflammation Lipopolysaccharides Male Mice, Inbred C57BL Mice, Transgenic Monoacylglycerol Lipases Neurons Oxidation-Reduction Prostaglandins

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