Topography of tetrahydrocannabinol in model membranes using neutron diffraction.
Small-angle neutron scattering was used to determine the intralamellar location of (-)-delta 8-tetrahydrocannabinol (delta 8-THC) in hydrated dipalmitoylphosphatidylcholine (DPPC) bilayers. Nuclear scattering density profiles were calculated from measurements on deuterium and non-deuterium-labelled inclusions (8.3% (w/w)) of delta 8-THC in DPPC multilayer samples. By comparing pairs of such nuclear density profiles, the locations of the deuterium labels were determined. Present results on the topography of delta 8-THC in membranes are compared with earlier X-ray measurements using iodine labelling. Whereas the position of the phenolic hydroxy group is similar in both types of measurement, a difference is found in the conformation of the terminal methyl groups of the cannabinoid side-chains. The X-ray measurements on dimyristoylphosphatidylcholine (DMPC) indicated that the iodine-labelled cannabinoid side-chains assume an all-trans orientation with the terminal iodine atom pointing inward into the membrane away from the tricyclic region while the neutron measurements indicate that the terminal CH3 group of delta 8-THC aligns itself at the level of the tricyclic ring system implying that the side chain exists in a more compact conformation perpendicular to the DPPC hydrocarbons. A Gaussian function analysis of the data indicates that the delta 8-THC molecule is significantly delocalized in the DPPC membrane in the liquid crystal phase. The mean location of delta 8-THC suggests that the active site on a membrane-embedded receptor protein will lie near the polar interface at the base of the phospholipid headgroups.
Chalk River Laboratories, AECL Research, Ontario, Canada.
P
P
Martel
A
A
Makriyannis
T
T
Mavromoustakos
K
K
Kelly
K R
KR
Jeffrey
D015060:1,2-Dipalmitoylphosphatidylcholine; D003903:Deuterium; D013759:Dronabinol / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008433:Mathematics; D008566:Membranes / Q000737:chemistry; D008968:Molecular Conformation; D009502:Neutrons; D013696:Temperature
D008051:Lipid Bilayers; D015060:1,2-Dipalmitoylphosphatidylcholine; D013759:Dronabinol; D003903:Deuterium