Avoiding the Raft: Losartan´s Affinity to Fluid Bilayers
We examined losartan’s action in different biomimetic membrane models. Losartan is an angiotensin II receptor antagonist mainly used for the regulation of high blood pressure, and structural details on its incorporation into the biomembrane interface have been studied by small angle X-ray scattering. We found that losartan tends to avoid cholesterol-rich membrane domains.
A. Hodzic et al. ,Phys. Chem. Chem. Phys. 14, 4780 (2012).
Figure 1. A possible scenario for losartan plasma membrane interactions is presented in panel E. Due to the denser lipid packing in the cholesterol rich rafts, losartan is likely to be excluded from this area, and preferentially found in the more fluid plasma membrane regions. Here losartan can accumulate and finally reach the AT1 receptor site. |
This indicates (i) a chain-saturation dependent competition of losartan with lipid-cholesterol interactions, and (ii) the insolubility of losartan in the liquid ordered phase of PCs. Consequently, losartan’s action is more likely to take place in fluid plasma membrane patches rather than in domains rich in cholesterol and saturated lipid species such as in membrane rafts.
Figure 2. Structural results overview: Schematic illustration of POPC (A) and DMPC (B) bilayer structure alterations induced by losartan. In both cases the up-take of losartan leads to membrane unbinding (losartan concentration xLos = 0.2). At very high cholesterol concentrations losartan still finds shelter in the POPC-Chol bilayer (C), whereas it gets expelled from DMPC–Chol membranes (D) (xChol = 0.4). Retrieve articleLosartan's affinity to fluid bilayers modulates lipid-cholesterol interactions; A. Hodzic, P. Zoumpoulakis, G. Pabst, T. Mavromoustakos, M. Rappolt Phys. Chem. Chem. Phys. 14, 4780 (2012); 10.1039/c2cp40134g |