FORMATION OF N-ACYL-PHOSPHATIDYLETHANOLAMINES AND N-ACYLETHANOLAMINES- PROPOSED ROLE IN NEUROTOXICITY

The formation of N-acyl-phosphatidylethanolamine (NAPE) and N-acyletha nolamine (NAE), including anandamide, in mammals in relation to neurot oxicity is discussed. Data on the characterization of the NAPE-forming N-acyltransferase, the NAPE-hydrolyzing phospholipase D, and the NAE- hydrolyzing amidase are reviewed. We suggest that NAPE and NAE, includ ing anandamide, are formed in neurons in response to the high intracel lular calcium concentrations that occur in injured neurons, e.g. due t o glutamate excitotoxicity. NAPE may have functions of its own besides being a precursor for NAE. The formation of both of these lipids may serve as a cytoprotective response, whether mediated by physical inter actions with membranes or enzymes, or mediated by activation of cannab inoid receptors. This suggestion implies that NAPE and NAE may have pa thophysiological roles in the brain. Whether these lipids also have ph ysiological roles is uncertain. (C) 1998 Elsevier Science Inc.