Effect of nitric oxide donors on membrane tritium accumulation of endocannabinoids and related endogenous lipids
(English)Manuscript (Other academic)
Endocannabinoids refers to a group of lipids with the ability of binding the two known cannabinoid receptors and synthesized by hydrolysis of lipid precursors. But still is the processing of the endocannabinoid metabolites following degradation poorly understood. Using tritium labelled anandamide (AEA) we discovered that nitric oxide (NO) donors significantly increased 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. In addition, utilizing AEA labelled in either the arachidonate or ethanolamine part of the molecule revealed that the effect of NO donors mainly involved the arachidonate part of the molecule. In enzyme studies, 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 diminished the effect produced by NO donors in cells with a large FAAH component, indicating that the effects were downstream of the enzyme. Similar results of the NO donors were also obtained when radiolabelled 2-arachidonoylglycerol (2-AG) was used. These data showed that the processing of endocannabinoid metabolites can be regulated by NO donors and may therefore be of importance in recycling lipid compounds to elevate the tissue levels.
Endocannabinoids; anandamide; nitric oxide; membrane accumulation; fatty acid amide hydrolase
Pharmacology and Toxicology
Research subject biokemisk farmakologi
IdentifiersURN: urn:nbn:se:umu:diva-22171OAI: oai:DiVA.org:umu-22171DiVA: diva2:213030