Topography and thermotropic properties of cannabinoids in brain sphingomyelin bilayers

In our previous publications we compared the locations of the biologically active (-)-Delta(8)-tetrahydrocannabinol (Delta(8)-THC) with that of its inactive analog O-methyl-(-)-Delta(8)-tetrahydrocannabinol (Me-Delta(8)-THC) in the liquid crystalline phase of partially hydrated dimyristoylphosphatidylcholine (DMPC) bilayers (Mavromoustakos et al. (1990) Biophys. Acta 1024, 336-344; Yang et al. (1993) Life Sci. 53, 117-122). Delta(8)-THC was shown to localize itself preferentially in the vicinity of the membrane interface with its phenolic hydroxyl group anchored near the carbonyl groups of DMPC while the more lipophilic Me-Delta(8)-THC is located deeper towards the center of the bilayer. In the present publication we studied and compared the topography of the two analogs in the gel phase of brain sphingomyelin bilayers. Again we found that Delta(8)-THC is located near the membrane interface approximately 15 Angstrom from the center of the bilayer while its inactive analog localizes deeper in the bilayer at an average site only 8 Angstrom from the center of the membrane bilayer. It thus, appears that both analogs preferentially localize in distinct sites within the membrane bilayer which are independent of the mesomorphic state and the nature of the phospholipid. Our results suggest that in the more complex environment of biological membrane which is composed of different phospholipids and proteins the two analogs are expected to prefer different average locations within the bilayer, a property which may in part explain the observed differences in their biological activities.