Faculty Collaboration Database

Effects of the cannabinoids on physical properties of brain membranes and phospholipid vesicles: fluorescence studies. J Pharmacol Exp Ther 1985 Mar;232(3):579-88

Date

03/01/1985

Pubmed ID

2983062

Scopus ID

2-s2.0-0021929098 (requires institutional sign-in at Scopus site)   95 Citations

Abstract

The effects of four cannabinoids on the physical properties of brain synaptic plasma membranes (SPM), lipid extracts of SPM and phospholipid vesicles were evaluated using fluorescence probes. In vitro, the psychoactive cannabinoids, delta 9-tetrahydrocannabinol (delta 9-THC) and 11-hydroxyl-delta 9-tetrahydrocannabinol (11-OH-delta 9-THC) at concentrations of 1 and 3 microM decreased polarization of the fluorescence emission of 1,6-diphenyl-1,3,5-hexatriene (DPH) in SPM. At the same concentrations, cannabidiol (CBD) and cannabinol, cannabinoids devoid of marijuana-like psychoactivity, had no effect on DPH polarization. The effects of 11-OH-delta 9-THC and CBD on vesicles made from lipids extracted from SPM were identical to their effects on intact SPM. These changes in DPH polarization were not due to changes in fluorescence lifetime and indicate that, at low concentrations, the psychoactive cannabinoids increase the rotational mobility of DPH in the membrane core. In contrast, in SPM-extracted lipids, both 11-OH-delta 9-THC and CBD decreased the mobility of stearic acid with an anthroyloxy label at both the second (2-AS) and twelfth (12-AS) carbon atoms. Studies of DPH polarization in various phosphatidylcholines (PC) demonstrated that the actions of the cannabinoids were dependent on initial bilayer fluidity. 11-OH-delta 9-THC was less effective at decreasing polarization of trimethylammonium DPH (TMA-DPH), a probe of the bilayer surface, than of DPH whereas CBD affected mobility of the two probes equally. Neither CBD nor 11-OH-delta 9-THC altered DPH mobility in phosphatidylethanolamine, phosphatidylserine vesicles. These findings indicate that the psychoactive cannabinoids increase fluidity in the hydrophobic core of brain membranes and support a membrane perturbant hypothesis of the mechanism of delta 9-THC action.

Author List

Hillard CJ, Harris RA, Bloom AS

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Brain Chemistry
Cannabidiol
Cannabinoids
Cannabinol
Dronabinol
Fluorescence Polarization
Lipid Bilayers
Male
Membrane Fluidity
Membrane Lipids
Mice
Mice, Inbred DBA
Phospholipids
Rats
Rats, Inbred Strains
Synaptic Membranes