Location and orientation of serotonin receptor 1a agonists in model and complex lipid membranes.
Magic angle spinning (MAS) NMR has been used to investigate the location and orientation of five serotonin receptor 1a agonists (serotonin, buspirone, quipazine, 8-OH-DPAT, and LY-163,165) in single component model lipid and brain lipid membranes. The agonist locations are probed by monitoring changes in the lipid proton chemical shifts and by MAS-assisted nuclear Overhauser enhancement spectroscopy, which indicates the orientation of the agonists with respect to the 1,2-dioleoyl-sn-glycero-3-phosphocholine lipids. In the single component bilayer, the membrane agonists are found predominantly in the top of the hydrophobic chain or in the glycerol region of the membrane. Most of the agonists orient approximately parallel to the membrane plane, with the exception of quipazine, whose piperazine ring is found in the glycerol region, whereas its benzene ring is located within the lipid hydrophobic chain. The location of the agonist in brain lipid membranes is similar to the 1,2-dioleoyl-sn-glycero-3-phosphocholine lipid bilayers; however, many of the agonists appear to locate close to the cholesterol in the membrane in preference to the phospholipids.
Lopez
Jakob J
JJ
Department of Chemistry, University of Hull, Hull, HU6 7RX, United Kingdom.
Lorch
Mark
M
D000818:Animals; D001923:Brain Chemistry; D002417:Cattle; D002784:Cholesterol / Q000737:chemistry*; D005990:Glycerol / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010767:Phosphorylcholine / Q000737:chemistry*; D017366:Serotonin Receptor Agonists / Q000737:chemistry*; D013552:Swine
D008051:Lipid Bilayers; D017366:Serotonin Receptor Agonists; D010767:Phosphorylcholine; D002784:Cholesterol; D005990:Glycerol