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 Ca(2+) transients and activation of cAMP response element-binding protein (CREB) were measured in the presence of tutin. Application of tutin (1-1000 microM) inhibited the glycinergic evoked current in a concentration-dependent manner. Moreover, the frequency of spontaneous Ca(2+) 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.
Fuentealba
Jorge
J
Department of Physiology, University of Concepcion, Chile. jorgefuentealba@udec.cl
Guzmán
Leonardo
L
Manríquez-Navarro
Paula
P
Pérez
Claudia
C
Silva
Mario
M
Becerra
José
J
Aguayo
Luis G
LG
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000302:isolation & purification / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis; D004594:Electrophysiology; D005260:Female; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D010947:Plants, Toxic / Q000737:chemistry; D011247:Pregnancy; D018009:Receptors, Glycine / Q000187:drug effects*; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
D000697:Central Nervous System Stimulants; D017362:Cyclic AMP Response Element-Binding Protein; D010852:Picrotoxin; D018009:Receptors, Glycine; D012717:Sesquiterpenes; C009614:tutin