Putative neuroprotective actions of N-acyl-ethanolamines.
N-Acyl-ethanolamines (NAEs) and their precursors, N-acyl-ethanolamine phospholipids (NAPEs), are present in the mammalian brain at levels of a few hundred picomoles/gram tissue and a few nanomoles/gram tissue, respectively. NAE-containing arachidonic acid is called anandamide, and it has attracted particular attention since it is a partial agonist for the cannabinoid receptors, for which 2-arachidonoylglycerol is the full agonist. In addition, anandamide may also activate the vanilloid receptor. Anandamide usually amounts to 1-10% of NAEs, as the vast majority of N-acyl groups are saturated and monounsaturated fatty acids. Formation of NAPE and NAE is catalyzed by an N-acyltransferase and an NAPE-hydrolyzing phospholipase D, respectively, two enzymes that have been characterized only preliminary. Interestingly, NAPEs and NAEs accumulate in the brain in response to neurodegenerative insults at a time when other phospholipids are subjected to rapid degradation. This is an important biosynthetic aspect of NAPE and NAE, as NAEs may be neuroprotective by a number of different mechanisms involving both receptor activation and non-receptor-mediated effects, e.g. by binding to cannabinoid receptors and interfering with ceramide turnover, respectively.
Department of Pharmacology, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen, Denmark. HSH@dfh.dk
Harald S
HS
Hansen
Birthe
B
Moesgaard
Gitte
G
Petersen
Henrik H
HH
Hansen
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D002518:Ceramides / Q000378:metabolism; D063388:Endocannabinoids; D004983:Ethanolamines / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000187:drug effects
D001095:Arachidonic Acids; D002518:Ceramides; D063388:Endocannabinoids; D004983:Ethanolamines; C022203:N-acylethanolamines; D018696:Neuroprotective Agents; D010743:Phospholipids; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C078814:anandamide