delta(9)-Tetrahydrocannabinol increases nerve growth factor production by prostate PC-3 cells. Involvement of CB1 cannabinoid receptor and Raf-1.
Cannabinoids, the active components of marihuana, exert a variety of effects in humans. Many of these effects are mediated by binding to two types of cannabinoid receptor, CB1 and CB2. Although CB1 is located mainly in the central nervous system, it may also be found in peripheral tissues. Here, we study the effect of cannabinoids in the production of nerve growth factor by the prostate tumor cell line PC-3. We show that addition of Delta(9)-tetrahydrocannabinol to PC-3 cells stimulated nerve growth factor production in a dose-dependent and time-dependent manner. Maximal effect was observed at 0.1 microM Delta(9)-tetrahydrocannabinol and 72 h of treatment. Stimulation was reversed by the CB1 antagonists AM 251 and SR 1411716A. Pre-treatment of cells with pertussis toxin also prevented the effect promoted by Delta(9)-tetrahydrocannabinol. These results indicate that Delta(9)-tetrahydrocannabinol stimulation of nerve growth factor production in these cells was mediated by the cannabinoid CB1 receptor. The implication of Raf-1 activation in the mode of action of Delta(9)-tetrahydrocannabinol is also suggested.
Velasco
L
L
Department of Biochemistry and Molecular Biology, University of Alcalá, Madrid, Spain.
Ruiz
L
L
Sánchez
M G
MG
Díaz-Laviada
I
I
D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D008297:Male; D020932:Nerve Growth Factor / Q000096:biosynthesis*; D037342:Pertussis Toxin; D010880:Piperidines / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011485:Protein Binding; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077285:Rimonabant; D013997:Time Factors; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005419:Flavonoids; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D010566:Virulence Factors, Bordetella; C103505:AM 251; D013759:Dronabinol; D020932:Nerve Growth Factor; D037342:Pertussis Toxin; D019908:Proto-Oncogene Proteins c-raf; D000077285:Rimonabant; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one