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CANNABINOID ENANTIOMER ACTION ON THE CYTOARCHITECTURE
Author(s) -
WILSON RONALD G.,
TAHIR STEPHEN K.,
MECHOULAM RAPHAEL,
ZIMMERMAN SELMA,
ZIMMERMAN ARTHUR M.
Publication year - 1996
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1006/cbir.1996.0019
Subject(s) - cytoplasm , cytoskeleton , microtubule , vacuole , actin , microfilament , biology , microbiology and biotechnology , cannabinoid , cytoarchitecture , cell , chemistry , biochemistry , anatomy , receptor
The negative and positive enantiomers of 7‐hydroxy‐ Δ 6 ‐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 μ m HU‐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 Δ 1 ‐THC on the cellular parameters studied reveals that in differentiating cells the action of Δ 1 ‐THC is intermediate between that of HU‐210 and HU‐211. This study demonstrates that compared to HU‐210 and Δ 1 ‐THC the positive enantiomer HU‐211 has little cellular activity.