Anandamide cellular uptake

Ortar G, Ligresti A, De Petrocelli,s L, Morera E, Di Marzo V (2003) Novel selective and metabohcally stable inhibitors of anandamide cellular uptake. Biochem Pharmacol 65 1473-1481... 

Fowler CJ, Tiger G, Ligresti A, Lopez-Rodriguez ML, Di Marzo V (2004) Selective inhibition of anandamide cellular uptake versus enzymatic hydrolysis—a difficult issue to handle. Eur J Pharmacol 492 1-11... 

Ortar, G., Ligresti, A., De Petrocellis, L., Morera, E. and Di Marzo, V., Novel selective and metabolically stable inhibitors of anandamide cellular uptake, Biochem Pharmacol, 65 P003) 1473-1481. 

The endocannabinoid anandamide also inhibits intestinal motility since it was shown to reduce both charcoal transit in the upper GIT (46) and glass bead transit in distal colon (49) via cannabinoid CBi receptors. In addition, a selective inhibitor of anandamide cellular uptake, VDMII, can inhibit colonic propulsion in a SR141716A-sensitive manner. However, a less selective anandamide uptake inhibitor, AM404, appears to be inactive on small intestine motUify in mice (4,49). 

Bisogno T, Hanus L, De Petrocellis L, TchUibon S, Ponde DE, Brandi I, Moriello AS, Davis JB, Mechoulam R, Di Marzo V (2001) Molecular targets for cannabidiol and its synthetic analogues effect on vanilloid VRl receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol 134 845-852... 

Deutsch DG, Glaser ST, Howell JM, Kunz JS, Puffenbarger RA, Hillard CJ, Abumrad N (2001) The cellular uptake of anandamide is coupled to its breakdown by fatty-acid amide hydrolase. J Biol Chem 276 6967-6973... 

Cannabidiol (CBD) is a non-psychotropic component of cannabis with possible therapeutic use as an anti-inflammatory drug. Recent studies on both enantiomers of CBD showed enantioselectivity in their interaction with cannabinoid and vanniloid (VRl) receptors as well as on the cellular uptake and enzymatic hydrolysis of anandamide (Bisogno et al. 2001). 

Indeed, AEA appears to be taken up by several cells via a facilitated transport mechanism, possibly mediated by a purported anandamide membrane transporter (AMT) (Fig. 4.3). In fact, cellular uptake of AEA is saturable, temperature-dependent and sensitive to synthetic inhibitors, as expected for a protein-mediated process (Maccarrone et al., 1998, Bisogno et al., 2001a). However, some authors have reported evidence against the existence of AMT,... 

FIGURE 24.2 Cellular uptake and enzymatic hydrolysis the major inactivation pathway of anandamide (AEiA) and 2-arachidonoyl-glycerol (2-AG). 

Inhibitors of Anandamide (AEA) Cellular Uptake Most Often Used In Vivo... 

The cellular uptake of anandamide is coupled to its breakdown by fatty-acid amide hydrolase. J Biol Chem. TIC. 6967-6973. 

Anandamide (AEA) is the most studied member of a new class of lipid mediators, collectively called endocannabinoids. The biological activity of AEA at cannabinoid and noncannabinoid receptors depends on its Hfe span in the extracellular space, which is regulated by a rapid cellular uptake, followed by intracellular degradation by the enzyme AEA hydrolase (fatty acid amide hydrolase). Here, we present the methodological details of the procedures that we have developed to assay fatty acid amide hydrolase activity and to characterize AEA transport through cell membranes in a new ideal ex vivo system like brain synaptosomes. 

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