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.