HEP (2005) 168:367–383
©cSpringer-Verlag 2005
Retrograde Signalling by Endocannabinoids
C.W. Vaughan · M.J. Christie ()
Pain Management Research Institute, Northern Clinical School,
University of Sydney at Royal North Shore Hospital, 2006 NSW,Sydney, Australia
[email protected]
1 Endocannabinoids ................................ 368
1.1 EndocannabinoidSynthesis,ReleaseandDegradation ............. 368
1.2 Endocannabinoids Act via Presynaptic Cannabinoid CB 1 Receptors
toInhibitTransmitterRelease........................... 369
2 Endocannabinoid as Retrograde Transmitters ................. 369
2.1 Depolarisation-Induced Transient,
Short-TermRetrogradeEndocannabinoidSignalling.............. 370
2.2 Activation of Postsynaptic Metabotropic Receptors
InducesShort-TermRetrogradeEndocannabinoidSignalling ......... 371
2.3 Activation of Postsynaptic Metabotropic Receptors
Potentiates Depolarisation-Induced Retrograde Endocannabinoid Signalling. 372
2.4 A Role for Retrograde Endocannabinoids in Long-Term Synaptic Plasticity.. 373
3 Production and Release of Endocannabinoids
in Retrograde Endocannabinoid Signalling................... 374
3.1 Ca2+-Dependent and Ca2+-IndependentEndocannabinoidProduction .... 374
3.2 Depolarisation and Stimulation/mGluR-Induced Depression:
DistinctIntracellularCascadesandEndocannabinoids? ............ 375
4 Spread of Retrograde Endocannabinoid Signalling............... 376
4.1 EndocannabinoidSignallingIsSpatiallyRestricted............... 376
4.2 FactorsInfluencingEndocannabinoidSpread.................. 376
4.3 InhibitorsofUptakeandMetabolism....................... 377
5 Other Endocannabinoid Targets: TRP Channels ................ 377
6 What Is the Functional Significance
of Retrograde Endocannabinoid Signalling?................... 378
7 Summary and Implications............................ 378
References ........................................ 380
AbstractThe cannabinoid neurotransmitter system comprises cannabinoid
G protein-coupled membrane receptors (CB 1 and CB 2 ), endogenous cannabinoids
(endocannabinoids), as well as mechanisms for their synthesis, membrane trans-
port and metabolism. Within the brain the marijuana constituent∆^9 -tetrahydro-
cannabinol (THC) produces its pharmacological actions by acting on cannabinoid
CB 1 receptors. THC modulates neuronal excitability by inhibiting synaptic trans-