title: Differences in receptor binding affinity of several phytocannabinoids do not explain their effects on neural cell cultures.
abstract: Phytocannabinoids are potential candidates for neurodegenerative disease treatment. Nonetheless, the exact mode of action of major phytocannabinoids has to be elucidated, but both, receptor and non-receptor mediated effects are discussed. Focusing on the often presumed structure-affinity-relationship, Ki values of phytocannabinoids cannabidiol (CBD), cannabidivarin (CBDV), cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN), THC acid (THCA) and THC to human CB1 and CB2 receptors were detected by using competitive inhibition between radioligand [(3)H]CP-55,940 and the phytocannabinoids. The resulting Ki values to CB1 range from 23.5 nM (THCA) to 14711 nM (CBDV), whereas Ki values to CB2 range from 8.5 nM (THC) to 574.2 nM (CBDV). To study the relationship between binding affinity and effects on neurons, we investigated possible CB1 related cytotoxic properties in murine mesencephalic primary cell cultures and N18TG2 neuroblastoma cell line. Most of the phytocannabinoids did not affect the number of dopaminergic neurons in primary cultures, whereas propidium iodide and resazurin formation assays revealed cytotoxic properties of CBN, CBDV and CBG. However, THC showed positive effects on N18TG2 cell viability at a concentration of 10 μM, whereas CBC and THCA also displayed slightly positive activities. These findings are not linked to the receptor binding affinity therewith pointing to another mechanism than a receptor mediated one. [Corrected]
authors.affiliation: Institute for Medical Biochemistry, University for Veterinary Medicine, Veterinaerplatz 1, A-1210 Vienna, Austria. Electronic address: sarah.rosenthaler@gmx.at.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rosenthaler
authors.affiliation: Institute for Medical Biochemistry, University for Veterinary Medicine, Veterinaerplatz 1, A-1210 Vienna, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Pöhn
authors.affiliation: Institute for Medical Biochemistry, University for Veterinary Medicine, Veterinaerplatz 1, A-1210 Vienna, Austria.
authors.forename: Caroline
authors.initials: C
authors.lastname: Kolmanz
authors.affiliation: Institute for Medical Biochemistry, University for Veterinary Medicine, Veterinaerplatz 1, A-1210 Vienna, Austria.
authors.forename: Chi Nguyen
authors.initials: CN
authors.lastname: Huu
authors.affiliation: Institute for Medical Biochemistry, University for Veterinary Medicine, Veterinaerplatz 1, A-1210 Vienna, Austria.
authors.forename: Christopher
authors.initials: C
authors.lastname: Krewenka
authors.affiliation: Institute for Medical Biochemistry, University for Veterinary Medicine, Veterinaerplatz 1, A-1210 Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Huber
authors.affiliation: Institute for Medical Biochemistry, University for Veterinary Medicine, Veterinaerplatz 1, A-1210 Vienna, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kranner
authors.affiliation: Institute for Medical Biochemistry, University for Veterinary Medicine, Veterinaerplatz 1, A-1210 Vienna, Austria.
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Rausch
authors.affiliation: Institute for Medical Biochemistry, University for Veterinary Medicine, Veterinaerplatz 1, A-1210 Vienna, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Moldzio
mesh_terms: D000818:Animals; D063386:Cannabinoid Receptor Agonists / Q000378:metabolism / Q000494:pharmacology*; D002186:Cannabinoids / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000032:analysis; D006801:Humans; D051379:Mice; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D043882:Receptors, Cannabinoid; D014446:Tyrosine 3-Monooxygenase; D005978:Glutathione
keywords: Cannabinoid receptors; Neural cell culture; Phytocannabinoids; Receptor binding affinity