Metabolic Fate of Platelet-Activating Factor in the Rat Enterocyte: The Role of a Specific Lysophospholipase D

Abstract The metabolism of platelet-activating factor (PAF) by isolated rat intestinal epithelial cells was investigated using 1-[ 3 H]octadecyl-2-acetyl- sn -glycero-3-phosphocholine. The principal metabolite produced by the cells was 1- O -alkylglycerol, which was found in association with the cells and the medium. When similar studies were conducted employing an intestinal epithelial cell line (INT 407), PAF was almost quantitatively converted into 1-alkyl-2-acyl- sn -glycero-3-phosphocholine (AAGPC). When the intestinal epithelial cell microsomes were incubated in the presence of fluoride to inhibit phosphohydrolase activity, the formation of 1-alkylglycerol was decreased in association with a stoichiometric increase in 1-alkylglycerophosphate, indicating the presence of a lysophospholipase D in the intestinal cells. When the phospholipase D activity was examined in the microsomal fraction prepared from intestinal epithelial cells, lyso-PAF was the preferred substrate and only trace amounts of lyso-PAF were converted into alkylacyl-GPC. Acyllyso-GPC was rapidly cleaved to form free fatty acids. The absence of lysophospholipase D activity in INT 407 cells cannot be attributed to the absence of brush border in these cells since no lysophospholipase D activity was present in isolated brush border preparations.