抄録
Muscarinic acetylcholine receptors are believed to play important roles in higher brain functions. Here we report that muscarinic activation suppresses inhibitory transmission through two distinct mechanisms, namely cannabinoid-dependent and -independent mechanisms. When cannabinoid CB1 receptor was blocked, oxotremorine M (oxo-M), a muscarinic agonist, suppressed IPSCs in a subset of hippocampal neuron pairs. This suppression was blocked by the M2-prefering antagonist gallamine, and totally absent in neuron pairs from M2-KO mice. When CB1 was not blocked, oxo-M suppressed IPSCs in a gallamine-resistant manner in cannabinoid-sensitive pairs. This suppression was blocked by the CB1 antagonist AM281, and completely eliminated in neuron pairs from M1/M3-KO mice. Our immunohistochemical examination showed that M2 and CB1 were present at different inhibitory presynaptic terminals. These results indicate that two distinct mechanisms mediate the muscarinic suppression. In a subset of synapses, activation of presynaptic M2 suppresses GABA release directly. In contrast, in a different subset of synapses, activation of postsynaptic M1/M3 induces the release of endocannabinoids that act on presynaptic CB1 receptors and suppress the GABA release. [Jpn J Physiol 54 Suppl:S150 (2004)]
