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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.JP

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.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2983062

Citation

Hillard, C J., et al. "Effects of the Cannabinoids On Physical Properties of Brain Membranes and Phospholipid Vesicles: Fluorescence Studies." The Journal of Pharmacology and Experimental Therapeutics, vol. 232, no. 3, 1985, pp. 579-88.
Hillard CJ, Harris RA, Bloom AS. Effects of the cannabinoids on physical properties of brain membranes and phospholipid vesicles: fluorescence studies. J Pharmacol Exp Ther. 1985;232(3):579-88.
Hillard, C. J., Harris, R. A., & Bloom, A. S. (1985). Effects of the cannabinoids on physical properties of brain membranes and phospholipid vesicles: fluorescence studies. The Journal of Pharmacology and Experimental Therapeutics, 232(3), 579-88.
Hillard CJ, Harris RA, Bloom AS. Effects of the Cannabinoids On Physical Properties of Brain Membranes and Phospholipid Vesicles: Fluorescence Studies. J Pharmacol Exp Ther. 1985;232(3):579-88. PubMed PMID: 2983062.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of the cannabinoids on physical properties of brain membranes and phospholipid vesicles: fluorescence studies. AU - Hillard,C J, AU - Harris,R A, AU - Bloom,A S, PY - 1985/3/1/pubmed PY - 1985/3/1/medline PY - 1985/3/1/entrez SP - 579 EP - 88 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 232 IS - 3 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/2983062/Effects_of_the_cannabinoids_on_physical_properties_of_brain_membranes_and_phospholipid_vesicles:_fluorescence_studies_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2983062 DB - PRIME DP - Unbound Medicine ER -