title: Differential effect of the benzophenanthridine alkaloids sanguinarine and chelerythrine on glycine transporters.
abstract: Glycine transporter inhibitors modulate the transmission of pain signals. Since it is well known that extracts from medicinal plants such as Chelidonium majus exhibit analgesic properties, we investigated the effects of alkaloids typically present in this plant on glycine transporters. We found that chelerythrine and sanguinarine selectively inhibit the glycine transporter GlyT1 with comparable potency in the low micromolar range while berberine shows no inhibition at all. At this concentration both alkaloids only minimally affected transport of the closely related glycine transporter GlyT2, suggesting that the effect is not mediated by the inhibitory activity of these alkaloids on the Na(+)/K(+) ATPase. GlyT1 inhibition was time-dependent, noncompetitive and increased with glycine concentration. While chelerythrine inhibition was reversible, the effect of sanguinarine was resistant to wash out. These results suggest that benzophenanthridine alkaloids interact with glycine transporters and at low micromolar range selectively target glycine transporter GlyT1.
authors.affiliation: Laboratory of Neurobiology, Institute of Molecular Biology, Slovak Academy of Sciences, Dubravska cesta 21, 842 51 Bratislava, Slovakia. Frantisek.Jursky@savba.sk
authors.forename: Frantisek
authors.initials: F
authors.lastname: Jursky
authors.forename: Martina
authors.initials: M
authors.lastname: Baliova
mesh_terms: D053119:Benzophenanthridines / Q000494:pharmacology*; D002460:Cell Line; D050487:Glycine Plasma Membrane Transport Proteins / Q000187:drug effects*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*
chemical_list: D053119:Benzophenanthridines; D050487:Glycine Plasma Membrane Transport Proteins; D007546:Isoquinolines; C005705:sanguinarine; C016299:chelerythrine