Cyclooxygenation of the arachidonoyl side chain of 1-arachidonoylglycerol and related compounds block their ability to prevent anandamide and 2-oleoylglycerol metabolism by rat brain in vitro

In the present study, the abilities of cyclooxygenated derivatives of 1-arachidonoylglycerol and related compounds to prevent the metabolism of [H-3](2)-oleoylglycerol and [H-3]anandamide by cytosolic and membrane fractions, respectively, have been investigated. For each compound, nine concentrations (range 0.2-100 mu M) were tested. 1-Arachidonoylglycerol inhibited the hydrolysis of [H-3]2-oleoylglycerol with a pI(50) value of 5.17 +/- 0.04 (maximum attainable inhibition 88%). In contrast, the 1-glyceryl esters of prostaglandin D-2, E-2 and F-2 alpha were very weak inhibitors of this hydrolysis. Similarly, prostaglandin D-2, prostaglandin D-2 ethanolamide and prostaglandin D-2 serinol amide produced < 20% inhibition of [H-3]2-oleoylglycerol metabolism at any concentration tested, in contrast to previous data with arachidonic acid, anandamide and arachidonoyl serinol which are all able to inhibit metabolism of this substrate under the assay conditions used here. A similar pattern was seen for all the compounds with respect to the inhibition of [H-3]anandamide hydrolysis by the membrane fractions. Thus, cyclooxygenation of the arachidonoyl side chain greatly reduces the ability of 1-arachidonoylglycerol and related compounds to inhibit the hydrolysis of [H-3]2-oleoylglycerol and [H-3]anandamide. (c) 2005 Elsevier Inc. All rights reserved.