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 effect s 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 ce ntral nervous system, it may also be found in peripheral tissues. Here, we study the effect of cannabinoids in the production of nerve growth factor b y the prostate tumor cell line PC-3. We show that addition of Delta (9)-tet rahydrocannabinol to PC-3 cells stimulated nerve growth factor production i n a dose-dependent and time-dependent manner. Maximal effect was observed a t 0.1 muM 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)-tetrahydroca nnabinol stimulation of nerve growth factor production in these cells was m ediated by the cannabinoid CB1 receptor. The implication of Raf-1 activatio n in the mode of action of Delta (9)-tetrahydrocannabinol is also suggested .