Potentiation and inhibition of glycine receptors by tutin.

Article Details

Citation

Copy to clipboard

Fuentealba J, Munoz B, Yevenes G, Moraga-Cid G, Perez C, Guzman L, Rigo JM, Aguayo LG

Potentiation and inhibition of glycine receptors by tutin.

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

PubMed ID

21044637 [ View in PubMed

]

Abstract

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 alpha(1) and alpha(2) homomeric GlyRs, with IC(50)s of 35 +/- 1 and 15 +/- 3 muM, respectively. The co-expression of alphabeta subunits reduced the potency of tutin, thus increasing the IC(50) to 51 +/- 4 and 41 +/- 8 muM for alpha(1)beta and alpha(2)beta 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 alpha1-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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ethanol	Glycine receptor subunit alpha-1	Protein	Humans	Yes	Agonist	Details