Abstract
Muscarinic acetylcholine (ACh) receptor activation presynaptically inhibited the putative striato-nigral GABAergic IPSC at substantia nigra pars reticulata (SNr) GABA neurons from young rats. This IPSC inhibition by muscarine was abolished by the application of M1- and M3-muscarinic ACh receptor antagonists, 4-DAMP and pirenzepine. On this inhibition, 4-DAMP was 100 times more potent than pirenzepine. The values of IC50 were 19 nM (4-DAMP) and 1.7 μM (pirenzepine), respectively. This result clearly indicated that muscarine activated the M3-receptors in this inhibition. Since it was reported that muscarine had its presynaptic effects through the production of cannabinoid (CB) at postsynaptic neurons in other parts of brain and that CB presynaptically inhibited the IPSC at SNr GABA neurons, the effect of a CB1-receptor antagonist, AM251, was observed. AM251 (5 μM) had no significant effect on the IPSC inhibition by muscarine. The mean values of the relative inhibition ratio were 0.529 ± 0.091 in control and 0.509 ± 0.085 in AM251 (mean ± s.e.m.; n=4, p=0.362). The activation of PKC by an activator (phorbol 12, 13-dibutyrate; PDBu, pretreatment for 15 min at 1 μM) did not mimic the effect of muscarine but significantly reduced the IPSC inhibition by muscarine. The mean values of the relative inhibition ratio were 0.449 ± 0.053 in control and 0.809 ± 0.102 in PDBu (n=4, p=0.008). This result might suggest the novel possibility that the M3-muscarinic ACh receptor activation negatively links the activation of PKC. [Jpn J Physiol 54 Suppl:S151 (2004)]
