Effects of the plant alkaloid sanguinarine on cation transport by human red blood cells and lipid bilayer membranes

Abstract

The plant alkaloid, sanguinarine, inhibits the ouabain-sensitive K -- Na pump and increases the downhill, ouabain-insensitive movements of K and Na in human red cells. These two effects have different temporal and concentration dependencies and are mediated by two different chemical forms of sanguinarine. The oxidized, charged form (5 X 10(-5) M) promptly inhibits the pump but does not affect leakage of K and Na. The reduced, uncharged form of sanguinarine causes lysis of red cells but does not inhibited the pump. Sanguinarine also increases the conductance of bilayers formed from sheep red cell lipids. The effect is produced by the uncharged but not by the charged form of sanguinarine. Bilayer conductance increases as the fourth power of sanguinarine concentration when the compound is present on both sides of the membrane and as the second power of concentration when present on only one side. Conductance also increase e-fold for each 34 mV increase in the potential difference imposed across the membrane. The results suggest that the uncharged forms of sanguinarine product voltage-dependent channels in bilayers.

Canonical Bcl-2 Motifs of the Na⁺/K⁺ Pump Revealed by the BH3 Mimetic Chelerythrine: Early Signal Transducers of Apoptosis?

“…Our findings may contribute to the elucidation of a more than 30 years old enigma: the related QBA sanguinarine inhibits NKA as well NKP in a variety of tissues [46,47,48,60,61,62] with similar dose dependence as observed here with CET in LECs. Some studies have shown that sanguinarine increases the in vitro dissociation constant of ouabain by 10 fold in guinea pig atrium preparations and exerts an inotropic effect [63], whereas inhibition of 3 H-ouabain binding in beef heart NKA is due to interaction with the ouabain receptor although a conformational change due to direct action was not excluded [46].…”

“…The preliminary observation that clotrimazole and apamin attenuated K + loss suggests that intermediate conductance Ca 2+ -activated K + channels (K + Ca 3.1, IK or Gardos channels) and small conductance SK channels may have been activated by CET. This finding means that the effect of CET in LECs is not due to breaching holes in the membrane bilayer as reported some 30 years ago in sanguinarine -treated human erythrocytes [60]. Interestingly, CET has been shown to block by 73 % the human P2X7 receptor through which extracellular ATP activates cation-selective channels with an IC 50 of 5.6 µM [72].…”

Surface-Enhanced Raman Spectroscopy (SERS) Tracking of Chelerythrine, a Na+/K+Pump Inhibitor, into Cytosol and Plasma Membrane Fractions of Human Lens Epithelial Cell Cultures

“…The CET structure-related sanguinarines have been known for a long time to inhibit the NKP in a variety of tissue preparations [11,12,13,14,15,16,17], without an explanation for this effect. Sequence homologies between BH1-like motifs originally reported to bind CET in Bcl-Xl proteins and found in the cytoplasmic aspect of the crystal structure of the NKP led to the hypothesis that CET may inhibit the NKP function through these BH1 motifs [10].…”

Dimethyl sulfoxide at high concentrations inhibits non-selective cation channels in human erythrocytes

“…The observed effect was not due to a decline in lipid cation conductance since Na Fig. 4 higher than that reported for Na + conductance (0.1 mol/l NaCl, pH 7.4) of pure lipid bilayers (Cala et al 1982).…”