In vitro activation of brain protein kinase C by the cannabinoids. Biochim Biophys Acta 1994 Jan 13;1220(2):163-70
Date
01/13/1994Pubmed ID
8312360DOI
10.1016/0167-4889(94)90131-7Scopus ID
2-s2.0-0028012276 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
The cannabinoids have been shown to affect both membrane lipid ordering and the activities of several membrane-associated proteins. We have investigated the effects of the cannabinoids on protein kinase C, a lipid-dependent enzyme that functions as an important regulator of signal-transduction processes in the brain. The naturally occurring cannabinoid delta 9-tetrahydrocannabinol (delta 9-THC) increased the activity of protein kinase C isolated from rat forebrain at concentrations of 10 microM and above. 11-OH-delta 9-THC, cannabinol and cannabidiol also increased protein kinase C activity in the same concentration range. delta 9-THC (10 microM) decreased the Kact of protein kinase C for calcium from 28 microM to 18 microM and had no effect on the phosphatidylserine concentration-stimulation relationship. At a concentration of 30 microM, delta 9-THC increased the binding of [3H]phorbol-12,13-dibutyrate ([3H]PDBu) to protein kinase C and decreased the Kd for [3H]PDBu from 8.2 nM to 5.4 nM. delta 9-THC also had effects on lipid ordering of PS micelles, producing a significant increase in the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene at a concentration of 10 microM. These data suggest that delta 9-THC activates protein kinase C via a novel mechanism, possibly as a result of effects on vesicle lipid physical characteristics.
Author List
Hillard CJ, Auchampach JAAuthors
John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinCecilia 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
AnimalsBinding Sites
Brain
Calcium
Cannabinoids
Dose-Response Relationship, Drug
Dronabinol
Enzyme Activation
Fluorescence Polarization
Male
Phosphatidylserines
Protein Kinase C
Rats
Rats, Sprague-Dawley
Up-Regulation
