Modulators of Endocannabinoid Enzymic Hydrolysisand Membrane Transport 205Lio YC, Reynolds LJ, Balsinde J, Dennis EA (1996) Irreversible inhibition of Ca(2+)-
independent phospholipase A2 by methyl arachidonyl fluorophosphonate. Biochim
Biophys Acta 1302:55–60
Lopez-Rodriguez ML, Viso A, Ortega-Gutierrez S, Lastres-Becker I, Gonzalez S, Fernandez-
Ruiz J, Ramos JA (2001) Design, synthesis and biological evaluation of novel arachidonic
acid derivatives as highly potent and selective endocannabinoid transporter inhibitors.
J Med Chem 44:4505–4508
Lopez-Rodriguez ML, Viso A, Ortega-Gutierrez S, Fowler CJ, Tiger G, de Lago E, Fernandez-
RuizJ,RamosJA(2003)Design,synthesisandbiologicalevaluationofnewendocannabi-
noid transporter inhibitors. Eur J Med Chem 38:403–412
Maccarrone M, Salvati S, Bari M, Finazzi A (2000a) Anandamide and 2-arachidonoylglycerol
inhibit fatty acid amide hydrolase by activating the lipoxygenase pathway of the arachi-
donate cascade. Biochem Biophys Res Commun 278:576–583
Maccarrone M, De Felici M, Bari M, Klinger F, Siracusa G, Finazzi-Agro A (2000b) Down-
regulation of anandamide hydrolase in mouse uterus by sex hormones. Eur J Biochem
267:2991–2997
Maccarrone M, Fiorucci L, Erba F, Bari M, Finazzi-Agro A, Ascoli F (2000c) Human mast
cells take up and hydrolyze anandamide under the control of 5-lipoxygenase and do not
express cannabinoid receptors. FEBS Lett 468:176–180
Maccarrone M, Valensise H, Bari M, Lazzarin N, Romanini C, Finazzi-Agro A (2001a) Pro-
gesterone up-regulates anandamide hydrolase in human lymphocytes: role of cytokines
and implications for fertility. J Immunol 166:7183–7189
Maccarrone M, De Petrocellis L, Bari M, Fezza F, Salvati S, Di Marzo V, Finazzi-Agro A
(2001b) Lipopolysaccharide downregulates fatty acid amide hydrolase expression and
increases anandamide levels in human peripheral lymphocytes. Arch Biochem Biophys
393:321–328
Maccarrone M, Bari M, Battista N, Finazzi-Agro A (2002) Estrogen stimulates arachi-
donoylethanolamide release from human endothelial cells and platelet activation. Blood
100:4040–4048
Maccarrone M, Di Rienzo M, Finazzi-Agro A, Rossi A (2003a) Leptin activates the anan-
damide hydrolase promoter in human T lymphocytes through STAT3. J Biol Chem
278:13318–13324
Maccarrone M, Bari M, Di Rienzo M, Finazzi-Agro A, Rossi A (2003b) Progesterone activates
fatty acid amide hydrolase (FAAH) promoter in human T lymphocytes through the
transcription factor Ikaros. Evidence for a synergistic effect of leptin. J Biol Chem
278:32726–32732
Maccarrone M, DeFelici M, Klinger FG, Battista N, Fezza F, Dainese E, Siracusa G, Finazzi-
Agro A (2004) Mouse blastocysts release a lipid which activates anandamide hydrolase
in intact uterus. Mol Hum Reprod 10:215–221
Maurelli S, Bisogno T, De Petrocellis L, Di Luccia A, Marino G, Di Marzo V (1995) Two
novel classes of neuroactive fatty acid amides are substrates for mouse neuroblastoma
’anandamide amidohydrolase’. FEBS Lett 377:82–86
McKinney MK, Cravatt BF (2003) Evidence for distinct roles in catalysis for residues of the
serine-serine-lysine catalytic triad of fatty acid amide hydrolase. J Biol Chem 278:37393–
37399
MechoulamR,FrideE,HanusL,SheskinT,BisognoT,DiMarzoV,BayewitchM,VogelZ
(1997) Anandamide may mediate sleep induction. Nature 389:25–26
Mendelson WB, Basile AS (1999) The hypnotic actions of oleamide are blocked by a cannabi-
noid receptor antagonist. Neuroreport 10:3237–3239
Ortar G, Ligresti A, De Petrocellis L, Morera E, Di Marzo V (2003) Novel selective and
metabolically stable inhibitors of anandamide cellular uptake. Biochem Pharmacol
65:1473–1481
Patel S, Wohlfeil ER, Rademacher DJ, Carrier EJ, Perry LJ, Kundu A, Falck JR, Nithipatikom
K, Campbell WB, Hillard CJ (2003) The general anesthetic propofol increases brain