Inhibition of Fatty Acid Amid Hydrolase, but not Monoacylglycerol lipase, Interfere with Cephalic Regeneration in Girardia tigrina

Undergraduate #72
Discipline: Biological Sciences
Subcategory: Cell and Molecular Biology

Shamara Wright - University of the District of Columbia
Co-Author(s): Kafayat Husband and Rosie Sneed, University of the District of Columbia, Washington, DC

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The endocannabinoid system is a major regulator of physiologic functions in mammals such as pain and memory. In previous studies in our laboratory, treatment with the synthetic cannabinoid WIN 55,212-2 inhibited cephalic regeneration in the North American brown planarian Girardia tigrina (Girard, 1850). To further define the role of endocannabinoids in planarians, we focused on the enzymes regulating breakdown of the endogenous cannabinoids, anandamide and 2arachidonylglycerol, the major mechanism by which the actions of endogenous cannabinoids are terminated in the body. Fatty acid amide hydrolase (FAAH) is specific for anandamide and related compounds while 2-arachidonyl glycerol is degraded by monoacylglycerol lipase (MAGL). We hypothesize that inhibition of endocannabinoid degradation will produce an effect similar to treatment with exogenous cannabinoids due to both prolongation of action and increased levels. Decapitated planarians were treated with either normal media, DMSO solvent control, PF-3845 (4.5 mM), URB597 (16 mM) (both inhibitors of FAAH), or KML29 (16 mM) (an inhibitor of MAGL) over a period of 5 days and the effects on cephalic regeneration were recorded. Planarians treated with either PF-3845 or URB597 had significantly reduced cephalic regeneration compared to controls; however, cephalic regeneration in KML29 -treated animals was very similar to controls. These data suggest that the primary endocannabionoid found in planarians is anandamide or a closely related compound. Future studies will seek to directly measure the levels of anandamide and the other ethanolamines thought to be significant in the endocannabinoid system.

Funder Acknowledgement(s): National Institute of Health (NIH); National Science Foundation (NSF). Supported by NIH Award T36GM101997-02

Faculty Advisor: Rosie Sneed,