EFFECTS OF THE CANNABINOIDS ON PHYSICAL-PROPERTIES OF BRAIN MEMBRANES AND PHOSPHOLIPID-VESICLES - FLUORESCENCE STUDIES

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 232  (3) , 579-588
Abstract
The effects of 4 cannabinoids on the physical properties of rat 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 .mu.M 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 2nd (2-AS) and 12th (12-AS) C 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 2 probes equally. Neither CBD nor 11-OH-.DELTA.9-THC altered DPH mobility in phosphatidylethanolamine, phosphatidylserine vesicles. 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.