Effect of angiotensin II non-peptide AT(1) antagonist losartan on phosphatidylethanolamine membranes

Losartan was found to affect both the thermotropic behavior and molecular m obility of dimyristoyl- and dipalmitoylphosphatidylcholine membranes (Theod oropoulou and Marsh, Biochim. Biophys. Acta 1461 (1999) 135-146). At low co ncentrations, the antagonist is located close to the interfacial region of the phosphatidylcholine bilayer while at high mole fractions it inserts dee per in the bilayers. In the present study, we investigated the interactions of losartan with phosphatidylethanolamine membranes using differential sca nning calorimetry (DSC), electron spin resonance (ESR) and P-31 nuclear mag netic resonance (NMR) spectroscopy. DSC showed that the antagonist affected the thermotropic transitions of dimyristoyl-, dipalmitoyl- and dielaidoyl- phosphatidylethanolamine membranes (DMPE, DPPE and DEPE, respectively). ESR spectroscopy showed that the interaction of losartan with phosphatidyletha nolamine membranes is more superficial than in the case of phosphatidylchol ine bilayers. Additionally, losartan increased the spin-spin broadening of 12-PESL spin labels in the gel phase of DMPE and DPPE membranes, while in t he case of DEPE membranes the opposite effect was observed. P-31-NMR showed that the antagonist stabilizes the fluid lamellar phase of DEPE membranes relative to the hexagonal HII phase. Our results show that losartan affects the thermotropic behavior of phosphatidylethanolamine membranes, while the molecular mobility of the membranes is not affected greatly. Furthermore, its interactions with phosphatidylethanolamine membranes are more superfici al than with phosphatidylcholine bilayers. (C) 2000 Elsevier Science B.V. A ll rights reserved.