Cholesterol and lipid phases influence the interactions between serotonin receptor agonists and lipid bilayers.
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.
Department of Chemistry, University of Hull, Hull HU6 7RX, United Kingdom and.
Rebecca
R
Batchelor
Christopher J
CJ
Windle
Sébastien
S
Buchoux
Mark
M
Lorch
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D021962:Membrane Microdomains / Q000737:chemistry*; D008956:Models, Chemical; D015233:Models, Statistical; D010879:Piperazines / Q000494:pharmacology; D011814:Quipazine / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry*; D017366:Serotonin Receptor Agonists / Q000737:chemistry* / Q000494:pharmacology; D013696:Temperature
D008051:Lipid Bilayers; D008055:Lipids; D010879:Piperazines; D043562:Receptors, G-Protein-Coupled; D017366:Serotonin Receptor Agonists; D015060:1,2-Dipalmitoylphosphatidylcholine; D011814:Quipazine; C044643:LY 165163; D002784:Cholesterol