Cholesterol and Lipid Phases Influence the Interactions between Serotonin Receptor Agonists and Lipid Bilayers

被引：4

作者：

Batchelor, Rebecca ^{[1
]}

Windle, Christopher J. ^{[1
]}

Buchoux, Sebastien ^{[2
]}

Lorch, Mark ^{[1
]}

机构：

[1] Univ Hull, Dept Chem, Kingston Upon Hull HU6 7RX, N Humberside, England

[2] Univ Picardie Jules Verne, F-80000 Amiens, France

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2010年 / 285卷 / 53期

基金：

英国工程与自然科学研究理事会;

关键词：

NUCLEAR-MAGNETIC-RESONANCE; NOESY NMR CROSSPEAKS; ANGLE-SPINNING NMR; SOLID-STATE NMR; HYDROCARBON CHAINS; H-2; NMR; DIPALMITOYL PHOSPHATIDYLCHOLINE; MEMBRANE INTERACTIONS; MOLECULAR DISORDER; ACYL CHAINS;

D O I：

10.1074/jbc.M110.155176

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Solid state NMR techniques have been used to investigate the effect that two serotonin receptor 1a agonists (quipazine and LY-165,163) have on the phase behavior of, and interactions within, cholesterol/phosphocholine lipid bilayers. The presence of agonist, and particularly LY-165,163, appears to widen the phase transitions, an effect that is much more pronounced in the presence of cholesterol. It was found that both agonists locate close to the cholesterol, and their interactions with the lipids are modulated by the lipid phases. As the membrane condenses into mixed liquid-ordered/disordered phases, quipazine is pushed up toward the surface of the bilayer, whereas LY-165,163 moves deeper into the lipid chain region. In light of our results, we discuss the role of lipid/drug interactions on drug efficacy.

引用

页码：41402 / 41411

页数：10

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