title: Cannabinoid enantiomer action on the cytoarchitecture.
abstract: The negative and positive enantiomers of 7-hydroxy-delta 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 microns) 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 microns 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 delta 1-THC on the cellular parameters studied reveals that in differentiating cells the action of delta 1-THC is intermediate between that of HU-210 and HU-211. This study demonstrates that compared to HU-210 and delta 1-THC the positive enantiomer HU-211 has little cellular activity.
authors.affiliation: Department of Zoology, University of Toronto, Canada.
authors.forename: R G
authors.initials: RG
authors.lastname: Wilson
authors.forename: S K
authors.initials: SK
authors.lastname: Tahir
authors.forename: R
authors.initials: R
authors.lastname: Mechoulam
authors.forename: S
authors.initials: S
authors.lastname: Zimmerman
authors.forename: A M
authors.initials: AM
authors.lastname: Zimmerman
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects; D000199:Actins / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects*; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008870:Microtubules / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D013237:Stereoisomerism; D014404:Tubulin / Q000235:genetics
chemical_list: D000199:Actins; D014404:Tubulin; D013759:Dronabinol; C062018:HU 211