Inhibitory effects of tutin on glycine receptors in spinal neurons.

Department of Physiology, University of Concepcion, Chile.
European Journal of Pharmacology (Impact Factor: 2.59). 04/2007; 559(1):61-4. DOI: 10.1016/j.ejphar.2006.12.018
Source: PubMed

ABSTRACT 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.

  • Radiotherapy and Oncology - RADIOTHER ONCOL. 01/2011; 99.
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    ABSTRACT: Over the last 150 years a number of people in New Zealand have been incapacitated, hospitalised, or died from eating honey contaminated with tutin, a plant-derived neurotoxin. A feature of the most recent poisoning incident in 2008 was the large variability in the onset time of clinical signs and symptoms of toxicity (0.5 to 17 h). To investigate the basis of this variability a pharmacokinetic study was undertaken in which 6 healthy males received a single oral dose of tutin-containing honey giving a tutin dose of 1.8μg/kg body weight. The serum concentration-time curve for all volunteers exhibited two discrete peaks with the second and higher level occurring at approximately 15 hours post-dose. Two subjects reported mild, transient headache at a time post-dose corresponding to maximum tutin concentrations. There were no other signs or symptoms typical of tutin intoxication such as nausea, vomiting, dizziness or seizures. Pharmacokinetic analysis using a two-site absorption model resulted in a good fit to the observed concentration data. A novel analytical method subsequently revealed the presence of glycoside conjugates of tutin in addition to unconjugated tutin in honey. These pharmacokinetic data will be important to better define a safe maximum tutin concentration in honey.
    Food and Chemical Toxicology. 07/2014; 72.
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    ABSTRACT: Seven homoserine-lactone (HL) acylated derivatives (HL1-HL7) were synthesized to determine the differences in antifeedant affects. The differences between these derivatives and tutin against Mythimna separata were tested. The structural assignments of these semisynthetic compounds were examined based on their infrared radiaion (IR), electrospray ionization mass spectrometry (ESIMS), and (1)H- and (13)C-nuclear magnetic resonance ((13)C-NMR) spectral data. Compound HL1 (N-(4-nitrobenzoyl)-homoserinelactone) is the optimized insecticidal agent among these compounds. In addition, the antifeedant activities between homoserinelactone and 7-hydroxycoumarin, tutin derivatives with the same acidylated substitutions were compared, which could help design and synthesize stronger novel botanical insecticides.
    Journal of Environmental Science and Health Part B Pesticides Food Contaminants and Agricultural Wastes 01/2013; 48(8):671-6. · 1.10 Impact Factor


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May 31, 2014