AbstractThe negative and positive enantiomers of 7‐hydroxy‐ Δ6‐tetrahydrocannabinol‐dimethylheptyl (designated HU‐210 and HU‐211 respectively) differentially affect undifferentiated and differentiating cultured pheochromocytoma cells (PC‐12 cells). In general, cell viability and cell proliferation were suppressed to a much greater extent with HU‐210 than with HU‐211 in differentiating cells. The effects of these synthetic cannabinoids on the cytoskeleton of PC‐12 cells were examined by epifluorescence and confocal microscopy. In both undifferentiated and differentiating PC‐12 cells, HU‐211 has little effect on the cytoarchitecture whereas HU‐210 disrupts the distribution of microtubules and microfilaments. Vacuoles (2–4 μm) were evident in the cytoplasm of HU‐210‐treated cells but not in the cytoplasm of HU‐211‐treated cells or in vehicle controls. Tubulin and actin mRNA levels were reduced to 5 and 40 , respectively (relative to untreated controls) in 10 μmHU‐210‐treated cells whereas the same concentration of HU‐211 reduced tubulin and actin mRNA levels to 90 and 95 , respectively. A comparison of the effects of the paired enantiomers and Δ1‐THC on the cellular parameters studied reveals that in differentiating cells the action of Δ1‐THC is intermediate between that of HU‐210 and HU‐211. This study demonstrates that compared to HU‐210 and Δ1‐THC
展开▼
