Cholesterol and lipid phases influence the interactions between serotonin receptor agonists and lipid bilayers

Batchelor, Rebecca; Windle, Christopher J.; Buchoux, Sébastien; Lorch, Mark

Abstract

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.

Citation

Batchelor, R., Windle, C. J., Buchoux, S., & Lorch, M. (2010). Cholesterol and lipid phases influence the interactions between serotonin receptor agonists and lipid bilayers. Journal of Biological Chemistry, 285(53), 41402-41411. https://doi.org/10.1074/jbc.M110.155176

• Journal Article Type: Article
• Acceptance Date: Oct 8, 2010
• Online Publication Date: Oct 20, 2010
• Publication Date: Dec 31, 2010
• Deposit Date: Nov 13, 2014
• Journal: Journal Of Biological Chemistry
• Print ISSN: 0021-9258
• Publisher: American Society for Biochemistry and Molecular Biology
• Peer Reviewed: Peer Reviewed
• Volume: 285
• Issue: 53
• Pages: 41402-41411
• DOI: https://doi.org/10.1074/jbc.M110.155176
• Keywords: Cell Biology; Biochemistry; Molecular Biology
• Public URL: https://hull-repository.worktribe.com/output/463426
• Contract Date: Nov 13, 2014