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Characterization of palmitoylethanolamide transport in mouse Neuro‐2a neuroblastoma and rat RBL‐2H3 basophilic leukaemia cells: comparison with anandamide
Author(s) -
Jacobsson Stig O P,
Fowler Christopher J
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704029
Subject(s) - palmitoylethanolamide , anandamide , fatty acid amide hydrolase , endocannabinoid system , biochemistry , cannabinoid , cannabinoid receptor , chemistry , arachidonic acid , 2 arachidonoylglycerol , cell culture , pharmacology , biology , receptor , agonist , enzyme , genetics
The endogenous cannabinoid receptor agonist anandamide (AEA) and the related compound palmitoylethanolamide (PEA) are inactivated by transport into cells followed by metabolism by fatty acid amide hydrolase (FAAH). The cellular uptake of AEA has been characterized in detail, whereas less is known about the properties of the PEA uptake, in particular in neuronal cells. In the present study, the pharmacological and functional properties of PEA and AEA uptake have been investigated in mouse Neuro‐2a neuroblastoma and, for comparison, in rat RBL‐2H3 basophilic leukaemia cells. Saturable uptake of PEA and AEA into both cell lines were demonstrated with apparent K M values of 28 μ M (PEA) and 10 μ M (AEA) in Neuro‐2a cells, and 30 μ M (PEA) and 9.3 μ M (AEA) in RBL‐2H3 cells. Both PEA and AEA uptake showed temperature‐dependence but only the AEA uptake was sensitive to treatment with Pronase and phenylmethylsulfonyl fluoride. The AEA uptake was inhibited by AM404, 2‐arachidonoylglycerol (2‐AG), R1‐ and S1‐methanandamide, arachidonic acid and olvanil with similar potencies for the two cell types. PEA, up to a concentration of 100 μ M , did not affect AEA uptake in either cell line. AEA, 2‐AG, arachidonic acid, R1‐methanandamide, Δ 9 ‐THC, and cannabidiol inhibited PEA transport in both cell lines. The non‐steroidal anti‐inflammatory drug indomethacin inhibited the AEA uptake but had very weak effects on the uptake of PEA. From these data, it can be concluded that PEA is transported in to cells both by passive diffusion and by a facilitated transport that is pharmacologically distinguishable from AEA uptake.British Journal of Pharmacology (2001) 132 , 1743–1754; doi: 10.1038/sj.bjp.0704029