Document Detail

Thermal, dynamic and structural properties of drug AT1 antagonist olmesartan in lipid bilayers.
MedLine Citation:
PMID:  21843501     Owner:  NLM     Status:  MEDLINE    
It is proposed that AT1 antagonists (ARBs) exert their biological action by inserting into the lipid membrane and then diffuse to the active site of AT1 receptor. Thus, lipid bilayers are expected to be actively involved and play a critical role in drug action. For this reason, the thermal, dynamic and structural effects of olmesartan alone and together with cholesterol were studied using differential scanning calorimetry (DSC), 13C magic-angle spinning (MAS) nuclear magnetic resonance (NMR), cross-polarization (CP) MAS NMR, and Raman spectroscopy as well as small- and wide angle X-ray scattering (SAXS and WAXS) on dipalmitoyl-phosphatidylcholine (DPPC) multilamellar vesicles. 13C CP/MAS spectra provided direct evidence for the incorporation of olmesartan and cholesterol in lipid bilayers. Raman and X-ray data revealed how both molecules modify the bilayer's properties. Olmesartan locates itself at the head-group region and upper segment of the lipid bilayers as 13C CP/MAS spectra show that its presence causes significant chemical shift changes mainly in the A ring of the steroidal part of cholesterol. The influence of olmesartan on DPPC/cholesterol bilayers is less pronounced. Although, olmesartan and cholesterol are residing at the same region of the lipid bilayers, due to their different sizes, display distinct impacts on the bilayer's properties. Cholesterol broadens significantly the main transition, abolishes the pre-transition, and decreases the membrane fluidity above the main transition. Olmesartan is the only so far studied ARB that increases the gauche:trans ratio in the liquid crystalline phase. These significant differences of olmesartan may in part explain its distinct pharmacological profile.
Dimitrios Ntountaniotis; Gregor Mali; Simona Golic Grdadolnik; Maria Halabalaki; Halabalaki Maria; Alexios-Leandros Skaltsounis; Constantinos Potamitis; Eleni Siapi; Petros Chatzigeorgiou; Michael Rappolt; Thomas Mavromoustakos
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-08-06
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1808     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-10-17     Completed Date:  2011-12-19     Revised Date:  2013-03-18    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  2995-3006     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
Department of Chemistry, University of Patras, Patras 26500, Greece.
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MeSH Terms
Calorimetry, Differential Scanning
Imidazoles / chemistry*
Lipid Bilayers*
Magnetic Resonance Spectroscopy
Receptor, Angiotensin, Type 2
Scattering, Radiation
Spectrum Analysis, Raman
Tetrazoles / chemistry*
Reg. No./Substance:
0/Imidazoles; 0/Lipid Bilayers; 0/Receptor, Angiotensin, Type 2; 0/Tetrazoles; 8W1IQP3U10/olmesartan
Erratum In:
Biochim Biophys Acta. 2012 May;1818(5):1436
Note: Maria, Halabalaki [corrected to Halabalaki, Maria]

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