Potentiation and inhibition of glycine receptors by tutin

Neuropharmacology. Feb-Mar 2011;60(2-3):453-9. doi: 10.1016/j.neuropharm.2010.10.023. Epub 2010 Oct 31.


In the present study we characterized the effects of the South American neurotoxin tutin on recombinant glycine receptors (GlyR) expressed in HEK 293 cells using whole-cell patch-clamp techniques. Tutin induced a concentration-dependent inhibition of α(1) and α(2) homomeric GlyRs, with IC(50)s of 35 ± 1 and 15 ± 3 μM, respectively. The co-expression of αβ subunits reduced the potency of tutin, thus increasing the IC(50) to 51 ± 4 and 41 ± 8 μM for α(1)β and α(2)β GlyRs, respectively. The inhibitory effect of tutin was competitive, independent of membrane potential and reversible suggesting a pore independent site. On the other hand, low tutin concentrations enhanced the current, which was not synergic with Zn(2+) or ethanol. A mutation in Lys385 altered ethanol but not tutin sensitivity, suggesting different sites for modulation of α1-containing GlyRs. Our results suggest that tutin affects the GlyR by a mechanism distinct to that of picrotoxin and ethanol, and that the pharmacological profile of tutin exhibits a "Zn-like" behaviour. In conclusion, these results provide information on molecular mechanisms important for understanding the toxic effects of a recently discovered South American neurotoxin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • HEK293 Cells
  • Humans
  • Picrotoxin / analogs & derivatives*
  • Picrotoxin / isolation & purification
  • Picrotoxin / metabolism
  • Picrotoxin / pharmacology
  • Plant Extracts / isolation & purification
  • Plant Extracts / metabolism
  • Plant Extracts / pharmacology*
  • Plant Leaves*
  • Protein Binding / physiology
  • Receptors, Glycine / agonists*
  • Receptors, Glycine / antagonists & inhibitors*
  • Receptors, Glycine / metabolism
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / metabolism
  • Sesquiterpenes / pharmacology*


  • Plant Extracts
  • Receptors, Glycine
  • Sesquiterpenes
  • Picrotoxin
  • tutin