Evidence for bidirectional endocannabinoid transport across cell membranes

Chicca, Andrea; Marazzi, Janine; Nicolussi, Simon; Gertsch, Jürg (2012). Evidence for bidirectional endocannabinoid transport across cell membranes. Journal of biological chemistry, 287(41), pp. 34660-82. Bethesda, Md.: American Society for Biochemistry and Molecular Biology 10.1074/jbc.M112.373241

Full text not available from this repository. (Request a copy)

Despite extensive research on the trafficking of anandamide (AEA) across cell membranes, little is known about the membrane transport of other endocannabinoids, such as 2-arachidonoylglycerol (2-AG). Previous studies have provided data both in favor and against a cell membrane carrier-mediated transport of endocannabinoids, using different methodological approaches. Because AEA and 2-AG undergo rapid and almost complete intracellular hydrolysis, we employed a combination of radioligand assays and absolute quantification of cellular and extracellular endocannabinoid levels. In human U937 leukemia cells, 100 nm AEA and 1 μm 2-AG were taken up through a fast and saturable process, reaching a plateau after 5 min. Employing differential pharmacological blockage of endocannabinoid uptake, breakdown, and interaction with intracellular binding proteins, we show that eicosanoid endocannabinoids harboring an arachidonoyl chain compete for a common membrane target that regulates their transport, whereas other N-acylethanolamines did not interfere with AEA and 2-AG uptake. By combining fatty acid amide hydrolase or monoacyl glycerol lipase inhibitors with hydrolase-inactive concentrations of the AEA transport inhibitors UCM707 (1 μm) and OMDM-2 (5 μm), a functional synergism on cellular AEA and 2-AG uptake was observed. Intriguingly, structurally unrelated AEA uptake inhibitors also blocked the cellular release of AEA and 2-AG. We show, for the first time, that UCM707 and OMDM-2 inhibit the bidirectional movement of AEA and 2-AG across cell membranes. Our findings suggest that a putative endocannabinoid cell membrane transporter controls the cellular AEA and 2-AG trafficking and metabolism.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Chicca, Andrea; Marazzi, Janine; Nicolussi, Simon and Gertsch, Jürg

ISSN:

0021-9258

Publisher:

American Society for Biochemistry and Molecular Biology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:37

Last Modified:

06 Dec 2013 13:37

Publisher DOI:

10.1074/jbc.M112.373241

PubMed ID:

22879589

Web of Science ID:

000309654200068

URI:

https://boris.unibe.ch/id/eprint/15053 (FactScience: 222212)

Actions (login required)

Edit item Edit item
Provide Feedback