TAILIEUCHUNG - Báo cáo khoa học: Uptake and metabolism of [3H]anandamide by rabbit platelets Lack of transporter?

Anandamide is an endogenous ligand for cannabinoid receptor and its protein-mediated transport across cellular membranes has been demonstrated in cells derived from brain as well as in cells of the immune system. This lipid is inactivated via intracellular degradation by a fatty acid amidohydrolase (FAAH). In the present study, we report that rabbit platelets, in contrast to human platelets, do not possess a carrier-mediated mechanism for the transport of [ 3 H]anandamide into the cell, . cellular uptake was not temperature dependent and its accumulation was not satu-rable. . | Eur. J. Biochem. 270 3498-3506 2003 FEBS 2003 doi Uptake and metabolism of 3H anandamide by rabbit platelets Lack of transporter Lambrini Fasia Vivi Karava and Athanassia Siafaka-Kapadai Department of Chemistry Biochemistry University of Athens Greece Anandamide is an endogenous ligand for cannabinoid receptor and its protein-mediated transport across cellular membranes has been demonstrated in cells derived from brain as well as in cells of the immune system. This lipid is inactivated via intracellular degradation by a fatty acid amidohydrolase FAAH . In the present study we report that rabbit platelets in contrast to human platelets do not possess a carrier-mediated mechanism for the transport of 3H anandamide into the cell . cellular uptake was not temperature dependent and its accumulation was not saturable. This endocannabinoid appears to enter the cell by simple diffusion. Once taken up by rabbit platelets 3H anandamide was rapidly metabolized into compounds which were secreted into the medium. Small amounts of free arachidonic acid as well as phospholipids were amongst the metabolic products. FAAH inhibitors did not decrease anandamide uptake whereas these compounds inhibited anandamide metabolism. In conclusion anandamide is rapidly taken up by rabbit platelets and metabolized mainly into water-soluble metabolites. Interestingly the present study also suggests the absence of a transporter for anand-amide in these cells. Keywords anandamide anandamide transporter fatty acid amidohydrolase rabbit platelets. Anandamide N-arachidonoylethanolamine is the most important member of a class of endogenous lipids called N-acylethanolamines that have been proposed as the physiological ligands for the cannabinoid CB receptors 1 2 . In addition to anandamide there is another endocannabinoid namely 2-arachidonoylglycerol that has been isolated from rat brain and canine gut 3 4 . For anandamide signaling via CB receptors an active uptake

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