Trifluoperazine Causes a Disturbance in Glycerophospholipid Monolayers Containing Phosphatidylserine (PS):  Effects of pH, Acyl Unsaturation, and Proportion of PS

Abstract

We have studied the interaction of trifluoperazine (TFP) with monolayers of various glycerophospholipids at 37 degrees C. TFP (1-10 microM) had little effect on surface pressure/molecular area isotherms in monolayers (on pure water) of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine but greatly increased the mean molecular area (mma) of dipalmitoylphosphatidylserine; the increment was greatest between 0 and 1 microM, and a further increase to 10 microM TFP gave only a slight increase in mma. With phosphatidylserine (PS)-containing stearoyl and varying acyls in the sn-1 and -2 positions, respectively, TFP increased the mma in a manner that depended on the number of double bonds and chain length. In mixtures of DPPC with two of these PS species the TFP-induced mma of the monolayers (on buffer, pH 7.4) increased linearly with the proportion of PS. Both PS and TFP have ionizable groups, and the TFP-induced mma increase had optima at pH 5.0 and 7.0. We conclude that the TFP-PS interaction is mainly, but not entirely, driven by electrostatic interactions between the TFP cation and PS headgroup anion, with an insertion of the phenothiazine moiety among the acyls in the monolayer that depends on the packing of the acyls.

Cholesterol regulates prokaryotic Kir channel by direct binding to channel protein

“…Furthermore, while it is known that TFP is a highly lipophilic drug that easily interacts with membrane lipids [35-37], our observations show that addition of TFP to liposomes containing no cholesterol has no effect on KirBac1.1 activity. We conclude, therefore, that the effect of TFP is to prevent cholesterol to bind and suppress KirBac1.1 channels.…”

Lipid-Sorting Specificity Encoded in K-Ras Membrane Anchor Regulates Signal Output

“…Fully saturated PtdSer is likely retained in cholesterol-rich complexes more extensively than asymmetric PtdSer (Bach et al, 1992; Maekawa and Fairn, 2015) concordant with the demonstration of a cholesterol-sensitive pool of PtdSer that does not interact with K-RasG12V (Cho et al, 2015). Moreover, membranes composed of asymmetric PtdSer sustain less perturbation when undergoing electrostatic interactions with external components than fully saturated PtdSer (Blois et al, 2006; Broniec et al, 2007). These biophysical properties may account for the preferential sorting of asymmetric PtdSer into K-RasG12V nanoclusters.…”

Interaction of acyclovir and its squalenoyl–acyclovir prodrug with DMPC in monolayers at the air/water interface

“…The phospholipids are spread on an aqueous subphase to permit a monomolecular distribution. If the monolayer is subjected to an area compression, the molecules distribution is modified and the molecules are forced to go from a "gaseous" or "liquid expanded" phase at low density to a "liquid condensed" phase at a higher density and, successively, to a "solid condensed" phase (Gaines, 1966;Mohwald, 1990;Prieto et al, 1998;Krasteva et al, 2000;Vollhardt and Fainerman, 2000;Broniec et al, 2007). Eventual variations in the behavior of the isotherms of the pure phospholipid, caused by the presence of a compound dispersed among the phospholipids on the aqueous surface can indicate anomalies in the perfect miscibility of the phospholipid/compound mixtures.…”