In this study we employed the neuroblastoma x glioma NG 108-15 cell line as a model for investigating the effects of long-term activation of cannabinoid receptors on δ opioid receptor desensitization, down-regulation and gene expression. Exposure of NG 108-15 cells to (-)-Δ9- tetrahydrocannabinol (Δ9-THC) reduced opioid receptor binding, evaluated in intact cells, by ≃ 40 - 45% in cells exposed for 24 h to 50 and 100 nM Δ9- THC and by ≃ 25 % in cells exposed to 10 nM Δ9-THC. Lower doses of Δ9- THC (0.1 and 1 nM) or a shorter exposure time to the cannabinoid (6 h) were not effective. Down-regulation of δ opioid receptors was not observed in cells exposed for 24 h to pertussis toxin (PTX) and then treated for 24 h with 100 nM Δ9-THC. In cells that were exposed for 24 h to the cannabinoid, the ability of Δ9-THC and of the δ opioid receptor agonist [D-Ser2, Leu5, Thr6]enkephalin to inhibit forskolin-stimulated cAMP accumulation was significantly attenuated. Prolonged exposure of NG 108-15 cells to 100 nM Δ9-THC produced a significant elevation of steady-state levels of δ opioid receptor mRNA. This effect was not observed in cells pretreated with PTX. The selective cannabinoid receptor antagonist SR 141716A blocked the effects elicited by Δ9-THC on δ opioid receptor desensitization, down-regulation and gene expression; thus indicating that these are mediated via activation of cannabinoid receptors. These data demonstrate the existence, in NG 108-15 cells, of a complex cross-talk between the cannabinoid and opioid receptors on prolonged exposure to Δ9-THC triggered by changes in signaling through G(i) and/or G0-coupled receptors.
Di Toro R., Campana G., Sciarretta V., Murari G., Spampinato S. (1998). Regulation of δ opioid receptors by Δ9-tetrahydrocannabinol in NG108- 15 hybrid cells. LIFE SCIENCES, 63(14), 197-204 [10.1016/S0024-3205(98)00390-7].
Regulation of δ opioid receptors by Δ9-tetrahydrocannabinol in NG108- 15 hybrid cells
Di Toro R.;Campana G.;Murari G.;Spampinato S.
1998
Abstract
In this study we employed the neuroblastoma x glioma NG 108-15 cell line as a model for investigating the effects of long-term activation of cannabinoid receptors on δ opioid receptor desensitization, down-regulation and gene expression. Exposure of NG 108-15 cells to (-)-Δ9- tetrahydrocannabinol (Δ9-THC) reduced opioid receptor binding, evaluated in intact cells, by ≃ 40 - 45% in cells exposed for 24 h to 50 and 100 nM Δ9- THC and by ≃ 25 % in cells exposed to 10 nM Δ9-THC. Lower doses of Δ9- THC (0.1 and 1 nM) or a shorter exposure time to the cannabinoid (6 h) were not effective. Down-regulation of δ opioid receptors was not observed in cells exposed for 24 h to pertussis toxin (PTX) and then treated for 24 h with 100 nM Δ9-THC. In cells that were exposed for 24 h to the cannabinoid, the ability of Δ9-THC and of the δ opioid receptor agonist [D-Ser2, Leu5, Thr6]enkephalin to inhibit forskolin-stimulated cAMP accumulation was significantly attenuated. Prolonged exposure of NG 108-15 cells to 100 nM Δ9-THC produced a significant elevation of steady-state levels of δ opioid receptor mRNA. This effect was not observed in cells pretreated with PTX. The selective cannabinoid receptor antagonist SR 141716A blocked the effects elicited by Δ9-THC on δ opioid receptor desensitization, down-regulation and gene expression; thus indicating that these are mediated via activation of cannabinoid receptors. These data demonstrate the existence, in NG 108-15 cells, of a complex cross-talk between the cannabinoid and opioid receptors on prolonged exposure to Δ9-THC triggered by changes in signaling through G(i) and/or G0-coupled receptors.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
