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This Article Full Text Full Text (PDF) All Versions of this Article: 572/3/735    most recent jphysiol.2006.105569v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sang, N. Articles by Chen, C. Search for Related Content PubMed PubMed Citation Articles by Sang, N. Articles by Chen, C. Related Collections Neuroscience

¹ Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA

The oxygenation of endogenous cannabinoids (eCBs) 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide by cyclooxygenase-2 (COX-2) produces novel types of prostanoids: prostaglandin glycerol esters (PG-Gs) and prostaglandin ethanolamides (PG-EAs). However, the physiological function of COX-2 oxidative metabolites of eCBs is still unclear. Here we demonstrate that PGE₂-G, a COX-2 oxidative metabolite of 2-AG, induced a concentration-dependent increase in the frequency of miniature inhibitory postsynaptic currents (mIPSCs) in primary cultured hippocampal neurons, an effect opposite to that of 2-AG. This increase was not inhibited by SR141716, a CB₁ receptor antagonist, but was attenuated by an IP₃ or MAPK inhibitor. In addition, we also examined the effects of other prostanoids derived from COX-2 oxygenation of eCBs on mIPSCs. PGD₂-G, PGF₂-G and PGD₂-EA, but not PGE₂-EA or PGF₂-EA, also increased the frequency of mIPSCs. The eCB-derived prostanoid-induced responses appeared to be different from those of corresponding arachidonic acid-derived prostanoids, implying that these effects are not mediated via known prostanoid receptors. We further discovered that the inhibition of COX-2 activity reduced inhibitory synaptic activity and augmented depolarization-induced suppression of inhibition (DSI), whereas the enhancement of COX-2 augmented the synaptic transmission and abolished DSI. Our results, which show that COX-2 oxidative metabolites of eCBs exert opposite effects to their parent molecules on inhibitory synaptic transmission, suggest that alterations in COX-2 activity will have significant impact on endocannabinoid signalling in hippocampal synaptic activity.

(Received 17 January 2006; accepted after revision 14 February 2006; first published online 16 February 2006)
Corresponding author C. Chen: Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite D, New Orleans, LA 70112, USA. Email: cchen{at}lsuhsc.edu

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