抄録
Marijuana affects neural functions through the binding of its active component to CB1 cannabinoid receptors. The CB1 receptor is widely distributed in the brain, and primarily localized on axons and presynaptic terminals. Endogenous ligands for cannabinoid receptors (endocannabinoids), such as anandamide and 2-arachidonoylglycerol, are lipid in nature, and produced on demand from membrane lipids through two enzymatic reactions. Recent studies have revealed that endocannabinoids play important roles in activity-dependent modulations of synaptic transmission as retrograde messengers. Endocannabinoids are released from postsynaptic neurons, retrogradely act on presynaptic CB1 receptors, and cause transient or long-lasting suppression of transmitter release. In this symposium, we summarize our studies with cultured hippocampal neurons, and show how the endocannabinoid signal is generated and terminated. We demonstrate the roles of voltage-gated Ca2+ channels, NMDA-type glutamate receptors, Gq/11-coupled receptors, and phospholipase Cβ in the generation, and the roles of monoacylglycerol lipase and cyclooxygenase-2 in the termination of the endocannabinoid signal. Wide distributions of these molecules as well as CB1 in the brain suggest importance of the endocannabinoid signal in various aspects of brain function. [J Physiol Sci. 2007;57 Suppl:S48]
