HEP (2005) 168:187–207
©cSpringer-Verlag 2005
Modulators of Endocannabinoid Enzymic Hydrolysis
and Membrane Transport
W.-S.V. Ho · C.J. Hillard ()
Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701
Watertown Plank Road, Milwaukee WI, 53226, USA
[email protected]
1Introduction.................................... 188
2 Fatty Acid Amide Hydrolase ........................... 189
2.1 CharacteristicsofFAAH.............................. 189
2.2 SubstrateSpecificityofFAAH........................... 190
2.3 MechanismsofFAAHRegulation ........................ 190
2.4 FAAHInhibitors.................................. 191
3MonoacylglycerolLipase............................. 194
3.1 BiochemicalandMolecularCharacteristicsofMGL............... 194
3.2 BrainMGL..................................... 194
3.3 SubcellularDistributionofMGL ......................... 195
3.4 SubstrateSpecificityofMGL ........................... 196
3.5 RegulationofMGLActivity............................ 197
3.6 MGLInhibitors .................................. 198
4 Endocannabinoid Transmembrane Movement ................. 198
4.1 Introduction.................................... 198
4.2 AEAUptakeInhibitors .............................. 199
5 Summary...................................... 201
References ........................................ 201
AbstractTissue concentrations of the endocannabinoidsN-arachidonoylethanol-
amine (AEA) and 2-arachidonoylglycerol (2-AG) are regulated by both synthesis
and inactivation. The purpose of this review is to compile available data regarding
three inactivation processes: fatty acid amide hydrolase, monoacylglycerol lipase,
and cellular membrane transport. In particular, we have focused on mechanisms
by which these processes are modulated. We describe the in vitro and in vivo
effects of inhibitors of these processes as well as available evidence regarding their
modulation by other factors.
KeywordsFatty acid amide hydrolase · Monoacylglycerol lipase · Transporter ·
Carrier · Anandamide · 2-Arachidonoylglycerol ·N-Arachidonoylethanolamine