Abstract
Small-angle neutron scattering was used to determine the intralamellar location of (—)- Δ 8-tetrahyrocannabinol ( Δ 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 Δ 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 Δ 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 dimyristoylphophatidylcholine (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 CH 3 group of Δ 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 Δ 8-THC molecule is significantly delocalized in the DPPC membrane in the liquid crystal phase. The mean location of Δ 8-THC suggests that the active site on membrane-embedded receptor protein will lie near the polar interface at the base of the phospholipid headgroups.
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