Brain levels of <Emphasis Type="Italic">N</Emphasis>-acylethanolamine phospholipids in mice during pentylenetetrazol-induced seizure |
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Authors: | Birthe?Moesgaard Henrik?H?Hansen Suzanne?L?Hansen Steen?Honore?Hansen Gitte?Petersen Email author" target="_blank">Harald?S?HansenEmail author |
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Affiliation: | (1) Department of Pharmacology, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, DK-2100 Copenhagen, Denmark;(2) Department of Analytical and Pharmaceutical Chemistry, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, DK-2100 Copenhagen, Denmark;(3) Lundbeck Limited, DK-2500 Copenhagen, Denmark |
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Abstract: | The N-acylethanolamine phospholipids (NAPE) are precursors for N-acylethanolamines (NAE), including anandamide (20∶4-NAE), which is a ligand for the cannabinoid receptors. Previously, NAPE
were believed to be found only in injured tissue, e.g., after neurodegenerative insults. Neuronal injury may occur in response
to seizure activity. Therefore, we investigated the effect of pentylenetetrazol (PTZ)-induced seizures in PTZ-kindled mice
on the level of NAPE in the brain. Male NMRI mice were kindled with PTZ injections 3 times/wk, thereby developing clonic seizures
in response to PTZ. Mice were killed within 30 min after the clonic seizure on the test day (12th injection) and the brains
were collected. Eight species of NAPE were analyzed as the glycerophospho-N-acylethanolamines by high-performance liquid chromatography-coupled electrospray ionization mass spectrometry. No effect
of the PTZ kindling on the NAPE levels in murine brains was observed. Total NAPE in control mice cortex (n=4) was 16.4±3.0 μmol/g wet weight of which 20∶4-NAPE accounted for 3.6 mol%, and the major species was 16∶0-NAPE, accounting
for 52.1 mol%. Determination of the activity of NAPE-hydrolyzing phospholipase D and of N-acyltransferase in brain membrane preparations from adult and 3-d-old mice revealed an enzyme pattern in the adult mice that
was favorable for NAE accumulation as opposed to NAPE accumulation. Thus, there was no difference in NAPE levels; at present,
however, this does not exclude that NAE may accumulate during seizure. |
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