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  • Title: Interactions of angiotensin II non-peptide AT(1) antagonist losartan with phospholipid membranes studied by combined use of differential scanning calorimetry and electron spin resonance spectroscopy.
    Author: Theodoropoulou E, Marsh D.
    Journal: Biochim Biophys Acta; 1999 Nov 09; 1461(1):135-46. PubMed ID: 10556495.
    Abstract:
    We used differential scanning calorimetry (DSC) and electron spin resonance (ESR) spectroscopy to investigate the interactions of Losartan, a potent, orally active Angiotensin II AT(1) receptor antagonist with phospholipid membranes. DSC results showed that Losartan sensitively affected the chain-melting behavior of dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) bilayer membranes. ESR spectroscopy showed that phosphatidylcholines spin-labeled at the 5-position of the sn-2 acyl chain (n-PCSL with n=5), incorporated either in DMPC or DPPC bilayers containing Losartan, were restricted in motion both in the gel and in the liquid-crystalline membrane phases, indicating a location of the antagonist close to the interfacial region of the phosphatidylcholine bilayer. At high drug concentrations (mole fraction >/= x=0.60), the decrease in chain mobility registered by 5-PCSL in fluid-phase membranes is smaller than that found at lower concentrations, whereas that registered by 14-PCSL is further increased. This indicates a different mode of interaction with Losartan at high concentrations, possibly arising from a location deeper within the bilayer. Additionally, Losartan reduced the spin-spin broadening of 12-PCSL spin labels in the gel-phase of DMPC and DPPC bilayers. As a conclusion, our study has shown that Losartan interacts with phospholipid membranes by affecting both their thermotropic behavior and molecular mobility.
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