Brodifacoum does not modulate human cannabinoid receptor-mediated hyperpolarization of AtT20 cells or inhibition of adenylyl cyclase in HEK 293 cells

摘要: BackgroundSynthetic cannabinoids are a commonly used class of recreational drugs that can have significant adverse effects. There been sporadic reports co-consumption illicit with rodenticides such as warfarin and brodifacoum (BFC) over the past 20 years but recently, hundreds people reported to poisoned mixture synthetic BFC. We sought establish whether BFC directly affects cannabinoid receptors, or their activation by CP55940 phytocannabinoid {Delta}9-tetrahydrocannabinol ({Delta}9-THC).nnMethodsThe effects on hyperpolarization wild type AtT20 cells, cells stably expressing human CB1- CB2-mediated were studied using fluorescent assay membrane potential. The CB1 CB2 mediated inhibition forskolin-stimulated adenylyl cyclase (AC) was measured BRET cAMP levels in HEK 293 CB2.nnResultsBFC did not activate affect produced somatostatin. (10 {micro}M) AtT20-CB1 AtT20-CB2 {Delta}9-THC. (1 AC activity CB2. also failed desensitization signalling prolonged (30 min) application {Delta}9-THC cells.nnDiscussionBFC is receptor agonist, appeared activation. Our data suggests there no pharmacodynamic rationale for mixing cannabinoids, however, it does speak may metabolism biodistribution. reasons underlying unknown, remains be established "contamination" deliberate accidental. However, consequences who ingested often serious, sometimes fatal, this seems unlikely due action at receptors.