1 research outputs found
Detection of Cyclooxygenase-2-Derived Oxygenation Products of the Endogenous Cannabinoid 2‑Arachidonoylglycerol in Mouse Brain
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