Molecular dynamics of the local anesthetic tetracaine in phospholipid vesicles.
Upon introduction into phosphatidylcholine vesicles, the 13C magnetic resonance peaks of the aromatic resonances of tetracaine are broadened while the T1 relaxation times show little change. Addition of tetracaine to vesicles containing 30% cholesterol produces a similar broadening in the 13C NMR spectrum of tetracaine. Nuclear magnetic resonance parameters of phosphatidylcholine in vesicles which are unchanged by the addition of equimolar tetracaine include 13C T1 relaxation time and 31P linewidth, T1 relaxation time, and nuclear Overhauser effect enhancement. These results are interpreted as indicating a hydrophobic interaction between hydrocarbon portions of the anesthetic and phospholipid bilayer. The rotational correlation time of tetracaine about its long axis in the vesicles has been calculated from the 13C NMR spin lattice relaxation times to be about 10(-10.3) s and is unchanged by incorporation into the phospholipid bilayer. The positively charged ammonium group of tetracaine interacts with the negatively charged phosphate group of the vesicle lipids. Using shift reagents and 31P NMR, tetracaine has been shown to displace cations from the bilayer surface, and does not undergo fast flip-flop across the vesicle bilayer.
Yeagle
P L
PL
Chemistry Department, University of Virginia, Charlottesville, Va 22901, USA.
Hutton
W C
WC
Martin
R B
RB
D000779:Anesthetics, Local / Q000032:analysis / Q000737:chemistry*; D000818:Animals; D001703:Biophysics / Q000379:methods*; D002412:Cations; D002845:Chromatography; D008051:Lipid Bilayers / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010063:Ovum / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013748:Tetracaine / Q000032:analysis / Q000737:chemistry*; D013997:Time Factors; D014867:Water / Q000737:chemistry
D000779:Anesthetics, Local; D002412:Cations; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D000644:Quaternary Ammonium Compounds; D014867:Water; D013748:Tetracaine