抄録
Endocannabinoids (eCBs) are lipid mediators and serve as retrograde messengers at synapses in various brain regions. eCBs are produced and released on demand in activity-dependent manners, bind to presynaptic CB1 receptors, and cause short- or long-term suppression of transmitter release. Previous studies have revealed that eCB-mediated retrograde synaptic suppression is induced by Ca2+ influx into postsynaptic neurons through voltage-gated Ca2+ channels. We tested whether Ca2+ entry through NMDA receptors (NMDARs) can trigger eCB release. Using cultured hippocampal neurons, we demonstrated that NMDA transiently suppressed cannabinoid-sensitive IPSCs. This NMDA-induced suppression was eliminated by blocking NMDARs and CB1 receptors, and was significantly reduced by intracellular BAPTA. These results indicate that NMDAR activation caused Ca2+ influx into postsynaptic neurons and induced eCB release. We then examined how released eCBs are degraded and eCB signaling is consequently terminated. We found that inhibition of monoacylglycerol lipase (MGL), a hydrolyzing enzyme of the major eCB 2-arachidonoylglycerol, markedly prolonged the suppression of IPSCs induced by Ca2+ influx. Together with the anatomical evidence for the localization of MGL in presynaptic terminals, our data indicate that presynaptic MGL contributes to termination of retrograde eCB signaling. [J Physiol Sci. 2008;58 Suppl:S17]
