In vitro activation of brain protein kinase C by the cannabinoids

• Published in: Biochimica et biophysica acta Vol. 1220; no. 2; pp. 163 - 170
• Main Authors: Hillard, Cecilia J., Auchampach, John A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 13.01.1994
• Subjects: Animals; Binding Sites; Brain - drug effects; Brain - enzymology; Calcium - pharmacology; Cannabinoid; Cannabinoids - pharmacology; Dose-Response Relationship, Drug; Dronabinol - pharmacology; Enzyme Activation - drug effects; Fluorescence Polarization; Forebrain; Male; Marijuana; Phorbol-12,13-dibutyrate; Phosphatidylserines - pharmacology; Protein kinase C; Protein Kinase C - isolation & purification; Protein Kinase C - metabolism; Rats; Rats, Sprague-Dawley; Up-Regulation; Δ9-Tetrahydrocannabinol; Forebrain; Phorbol-12,13-dibutyrate; Marijuana; Protein kinase C; Cannabinoid; Δ 9-Tetrahydrocannabinol
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/0167-4889(94)90131-7

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 Δ 9-tetrahydrocannabiol ( Δ 9-THC) increased the activity of protein kinase C isolated from rat forebrain at concentrations of 10 μM and above. 11-OH- Δ 9-THC, cannabinol and cannabidiol also increased protein kinase C activity in the same concentration range. Δ 9-THC (10 μM) decreased the K act of protein kinase C for calcium from 28 μM to 18 μM and had no effect on the phosphatidylserine concentration-stimulation relationship. At a concentration of 30 μM, Δ 9-THC increased the binding of [ 3H]phorbol-12,13-dibutyrate ([ 3H]PDBu) to protein kinase C and decreased the K d for [ 3H]PDBu from 8.2 nM to 5.4 nM. Δ 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 μM. These data suggest that Δ 9-THC activates protein kinase C via a novel mechanism, possibly as a result of effects on vesicle lipid physical characteristics.