Reference : Bisindole alkaloids from Strychnos guianensis are effective antagonists of nicotinic ...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/4625
Bisindole alkaloids from Strychnos guianensis are effective antagonists of nicotinic acetylcholine receptors in cultured human TE671 cells
English
Wins, Pierre [> > > >]
Margineanu, Ilca [> > > >]
Penelle, Jacques [> > > >]
Angenot, Luc mailto [Université de Liège - ULg > Département de pharmacie > Pharmacognosie >]
Grisar, Thierry mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique]
Bettendorff, Lucien mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique >]
2003
Naunyn-Schmiedeberg's Archives of Pharmacology
Springer-Verlag
367
3
253-259
Yes (verified by ORBi)
International
0028-1298
New York
[en] Strychnos guianensis ; indole alkaloids ; bisquaternary compounds ; curarizing agents ; nicotinic acetylcholine receptor ; ion fluxes ; TE 671 cell line
[en] Several mono- and bisindole quaternary alkaloids isolated from the stem bark of Strychnos guianensis have recently been shown to be effective blockers of neuromuscular transmission in mice. In this study, we used a human clonal cell line (TE671) expressing muscle-type nicotinic acetylcholine receptors. The agonist carbamylcholine activated a receptor-mediated Rb-86(+) efflux and this activation was antagonized by the indole alkaloids, the most active being bisindole bisquaternary compounds. The most effective antagonist, guiachrysine, had an IC50 around 0.43 muM in the presence of 0.5 mM carbamylcholine, compared to 0.16 muM for d-tubocurarine, the most potent curarizing alkaloid. Guiaflavine and 5',6'-dehydroguiaflavine were slightly less effective. Monoindole compounds were 10 to 100 times less potent than bisindole alkaloids. Kinetic analysis showed that the inhibition of the carbamylcholine-dependent Rb-86(+) efflux by guiaflavine was of mixed competitive and uncompetitive type. The competitive component (K-I = 0.21 muM) is presumably due to binding at the acetylcholine site, while the uncompetitive component (K'(I) = 0.92 muM) may be due to open channel block.
http://hdl.handle.net/2268/4625

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