Effect of nitric oxide donors on membrane tritium accumulation of endocannabinoids and related endogenous lipids.

Abstract:

:The endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are metabolised by cells by hydrolysis to arachidonic acid followed by esterification into phospholipids. Here, we report that nitric oxide (NO) donors significantly increase the amount of tritium accumulated in the cell membranes of RBL2H3 rat basophilic cells, 3T3-L1 mouse fibroblast cells and b.End5 mouse brain endothelioma cells following incubation of the intact cells with AEA labelled in the arachidonate part of the molecule. Similar results were seen with 2-AG and with arachidonic acid, whilst the NO donors reduced the accumulation of tritium after incubation of RBL2H3 cells with AEA labelled in the ethanolamine part of the molecule. Pretreatment of intact cells with NO donors did not increase the activity of the enzyme mainly responsible for metabolism of AEA, fatty acid amide hydrolase (FAAH). Furthermore, inhibition of FAAH completely blocked the effect produced by NO donors in cells with a large FAAH component, suggesting that for AEA, the effects were downstream of the enzyme. These data raise the possibility that the cellular processing of endocannabinoids following its uptake can be regulated by nitric oxide.

journal_name

Eur J Pharmacol

authors

Thors L,Fowler CJ

doi

10.1016/j.ejphar.2009.08.028

subject

Has Abstract

pub_date

2009-10-25 00:00:00

pages

10-8

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(09)00715-8

journal_volume

621

pub_type

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