Stability of prostaglandin glycerol esters in neuronal tissue

BIOL 157

Andrew Vila, andrew.vila@vanderbilt.edu1, Satish Kathuria2, Daniele Piomelli, piomelli@uci.edu2, and Lawrence J. Marnett, larry.marnett@vanderbilt.edu1. (1) Department of Biochemistry, Vanderbilt University School of Medicine, 23rd Ave at Pierce, Nashville, TN 37232, (2) Department of Pharmacology, University of California, 360 MSR II, Irvine, CA 92697
Cyclooxygenase-2 (COX-2) can oxygenate the endocannabinoids (EC's), arachidonylethanolamide (AEA) and 2-arachidonylglycerol (2-AG), to prostaglandin-ethanolamide (PGH2-EA) and -glycerol ester (PGH2-G) species, respectively. PGH2-EA and PGH2-G are metabolized by prostaglandin synthases to produce analogs of PGE2, PGD2, PGF2α, and PGI2, (but not TxA2). COX-2 may participate in regulating EC levels in neurons during retrograde signaling or produce novel metabolites for receptor activation. EC's metabolizing enzymes are important regulators of EC action, so we tested PG-G's stability to hydrolysis by esterases in dog brain. Crude brain homogenate rapidly hydrolyzed PG-G's to their respective free acids (t1/2 ~ 40-90 seconds for PGE2G, D2-G, and F2α-G). Partial purification of PG-G hydrolase activity from brain cytosol increased the specific activity 80-fold. Monoacylglycerol lipase preferentially hydrolyzes 2-AG over PG-G's (30-100-fold), suggesting this enzyme does not degrade PG-G's in vivo. Presence of a specific hydrolase in brain would suggest PG-G's possess a biological function in neuronal tissue.
 

Chemistry and Metabolism
4:30 PM-6:30 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster

Division of Biological Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006