Studies on the thermotropic effects of cannabinoids on phosphatidylcholine bilayers using differential scanning calorimetry and small angle X-ray diffraction.
We have studied the thermotropic properties of a wide variety of cannabinoids in DPPC bilayers. The molecules under study were divided into four classes: (a) classical cannabinoids possessing a phenolic hydroxyl group; (b) delta9-THC metabolites with an additional hydroxyl group on the C ring; (c) non-classical cannabinoids, and (d) cannabinoids with a protected phenolic hydroxyl group. The results showed that the first three groups have similar effects on the thermotropic properties of DPPC bilayers up to x = 0.05 (molar ratio) and that these effects do not parallel their biological activity. For concentrations less than x = 0.01, cannabinoids affect mainly the pretransition temperature in a progressive manner until its final abolishment. At x = 0.05, they further affect the main phase transition by lowering its phase transition temperature and broadening its half width. At high concentrations the thermograms have multiple components, indicating that membranes are no longer homogeneous but rather consist of different domains. At these concentrations cannabinoids with more hydroxyl groups give simpler thermograms. Low concentrations of cannabinoids in group d affect significantly the pretransition temperature, while high concentrations affect only marginally the main phase transition by slightly lowering its temperature and broadening its half width. These results point out the importance of the phenolic hydroxyl group in inducing membrane perturbations. The d-spacing data from our small angle X-ray diffraction experiments show that delta8-THC produces significant structural changes in the lipid bilayer, including the gel-phase tilting angle, the intermolecular cooperativity and the gauche:trans conformer ratio. Conversely, the inactive analog Me-delta8-THC does not cause drastic changes to the bilayer structure.
Mavromoustakos
T
T
National Hellenic Research Foundation, Institute of Organic and Pharmaceutical Chemistry, Athens, Greece.
Theodoropoulou
E
E
Papahatjis
D
D
Kourouli
T
T
Yang
D P
DP
Trumbore
M
M
Makriyannis
A
A
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002186:Cannabinoids / Q000737:chemistry / Q000494:pharmacology*; D008051:Lipid Bilayers / Q000737:chemistry*; D015394:Molecular Structure; D013816:Thermodynamics; D014961:X-Ray Diffraction
D002186:Cannabinoids; D008051:Lipid Bilayers; D015060:1,2-Dipalmitoylphosphatidylcholine