Human mast cells take up and hydrolyze anandamide under the control of 5-lipoxygenase and do not express cannabinoid receptors.
Human mast cells (HMC-1) take up anandamide (arachidonoyl-ethanolamide, AEA) with a saturable process (K(m)=200+/-20 nM, V(max)=25+/-3 pmol min(-1) mg protein(-1)), enhanced two-fold over control by nitric oxide-donors. Internalized AEA was hydrolyzed by a fatty acid amide hydrolase (FAAH), whose activity became measurable only in the presence of 5-lipoxygenase, but not cyclooxygenase, inhibitors. FAAH (K(m)=5.0+/-0.5 microM, V(max)=160+/-15 pmol min(-1) mg protein(-1)) was competitively inhibited by palmitoylethanolamide. HMC-1 cells did not display a functional cannabinoid receptor on their surface and neither AEA nor palmitoylethanolamide affected tryptase release from these cells.
Maccarrone
M
M
Department of Experimental Medicine, University of Rome, Tor Vergata, Via di Tor Vergata 135, 00133, Rome, Italy.
Fiorucci
L
L
Erba
F
F
Bari
M
M
Finazzi-Agrò
A
A
Ascoli
F
F
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000577:Amides; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001095:Arachidonic Acids / Q000493:pharmacokinetics*; D001667:Binding, Competitive; D001692:Biological Transport / Q000187:drug effects; D002186:Cannabinoids / Q000493:pharmacokinetics; D002460:Cell Line; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D063388:Endocannabinoids; D004983:Ethanolamines; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008407:Mast Cells / Q000378:metabolism*; D010169:Palmitic Acids / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000032:analysis; D014316:Tritium; D002722:Chlorobenzenes
D015117:5,8,11,14-Eicosatetraynoic Acid; D000577:Amides; D001094:Arachidonate 5-Lipoxygenase; D001095:Arachidonic Acids; D002186:Cannabinoids; D016861:Cyclooxygenase Inhibitors; D063388:Endocannabinoids; D004983:Ethanolamines; D007052:Ibuprofen; D007211:Indoles; D007213:Indomethacin; D016859:Lipoxygenase Inhibitors; D010169:Palmitic Acids; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D014316:Tritium; C060893:MK-886; D002722:Chlorobenzenes; C005958:palmidrol; C078814:anandamide