Anandamide facilitated transport

Melck, D., Bisogno, T, De Petrocellis, L, Chuang, H., Julius, D., Bifulco, M., and Di Marzo, V. (1999) Unsaturated long-chain N-acyl-vanillyl-amides (N-AVAMs) vanilloid receptor ligands that inhibit anandamide-facilitated transport and bind to CBl cannabinoid receptors. Biochem Biophys Res Commn. 262 275-284. 

De Petrocellis L, Bisogno T, Maccarrone M, Davis JB, Finazzi-Agro A, Di Marzo V (2001a) The activity of anandamide at vanilloid VRl receptors requires facilitated transport across the cell membrane and is limited by intracellular metabolism. J Biol Chem 276 12856-12863... 

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,... 

Anandamide is inactivated in two steps, first by transport inside the cell and subsequently by intracellular enzymatic hydrolysis. The transport of anandamide inside the cell is a carrier-mediated activity, having been shown to be a saturable, time- and temperature-dependent process that involves some protein with high affinity and specificity for anandamide (Beltramo, 1997). This transport process, unlike that of classical neurotransmitters, is Na+-independent and driven only by the concentration gradient of anandamide (Piomelli, 1998). Although the anandamide transporter protein has not been cloned yet, its well characterized activity is known to be inhibited by specific transporter inhibitors. Reuptake of 2-AG is probably mediated by the same facilitating mechanism (Di Marzo, 1999a,b Piomelli, 1999). 

Anandamide can be transported inside neural cells (neurons and glia) by a carrier-mediated facilitate diffusion mechanism (Beltramo et al., 1997) and transformed through two main pathways (1) hydrolysis to arachidonic acid and ethanolamine, and (2) oxidation to various oxygenated derivatives. 

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