Inhibitory effects of tutin on glycine receptors in spinal neurons

We studied the effects of tutin, a sesquiterpenoid obtained from Coriaria ruscifolia subspecie ruscifolia, a native poisonous Chilean plant, on spinal glycine receptors using patch clamp recordings. In addition, cytosolic Ca2+ transients and activation of cAMP response element-binding protein (CREB) were measured in the presence of tutin. Application of tutin (1–1000 μM) inhibited the glycinergic evoked current in a concentration-dependent manner. Moreover, the frequency of spontaneous Ca2+ spikes and spontaneous synaptic activity (AMPAergic events) was augmented and correlated with an increase in phosphorylated CREB levels, suggesting an enhancement in neuronal excitability. These results may explain the toxic effects of the plant characterized by seizures and convulsions with subsequent coma and death seen in humans and mice.