Formation of N-acyl-phosphatidylethanolamine and N-acylethanolamine (including anandamide) during glutamate-induced neurotoxicity.
N-Acyl-phosphatidylethanolamine (NAPE) is present in very small amounts in mammalian tissues (less than 0.1% of total phospholipids). However, NAPE as well as its degradation product, N-acylethanolamine (NAE), can be formed in certain neuronal tissues in response to increased [Ca2+]i. A high [Ca2+]i will activate the NAPE-forming N-acyltransferase using the sn-1 acyl group of a donor phospholipid as substrate in the transfer reaction. This membrane-bound enzyme seems to have no substrate specificity with respect to transfer of acyl groups; thus the fatty acids in the N-acyl group of NAPE are mainly 16:0 and 18:1, corresponding to the fatty acids in the sn-1 acyl group of the donor phospholipids. The NAPE-hydrolyzing phospholipase D also seems not to be acyl-group specific. In mouse neocortical neurons in primary culture, formation of NAPE and NAE is stimulated by glutamate via activation of the N-methyl-D-aspartate-receptor. Both NAPE and, to a lesser extent, NAE accumulate in a linear fashion for many hours while at the same time the neurons are dying. Likewise, in neurons prelabeled with 14C-arachidonic acid, 14C-arachidonic acid-labeled NAPE, and anandamide (= N-arachidonoylethanolamine) are accumulating. The formation of NAPE and NAE may represent a cytoprotective response in relation to various forms of neurotoxicity.
Department of Pharmacology, The Royal Danish School of Pharmacy, Copenhagen. HSH@mail.dfh.dk
H S
HS
Hansen
B
B
Moesgaard
H H
HH
Hansen
A
A
Schousboe
G
G
Petersen
D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D063388:Endocannabinoids; D004983:Ethanolamines / Q000378:metabolism*; D018698:Glutamic Acid / Q000633:toxicity*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity*; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism; D053284:Polyunsaturated Alkamides
D001095:Arachidonic Acids; D063388:Endocannabinoids; D004983:Ethanolamines; C022203:N-acylethanolamines; D009498:Neurotoxins; D010714:Phosphatidylethanolamines; D053284:Polyunsaturated Alkamides; D016718:Arachidonic Acid; D018698:Glutamic Acid; D000217:Acyltransferases; D010739:Phospholipase D; D002118:Calcium; C078814:anandamide