MED1101: A new dialdehydic compound regulating P2×7 receptor cell surface expression in U937 cells

摘要: Background information P2×7R is a member of the ionotropic family purinergic receptors activated by millimolar concentrations extracellular ATP such as induced inflammatory stimuli. The receptor widely expressed in cells haematopoietic origin monocytes, macrophages and microglia. There growing interest anta-gonist compounds P2×7R since it has been demonstrated to be viable therapeutic target for diseases. Here, we tested possible P2×7 antagonist effect MED1101, newly synthesised dialdehydic compound on U937 monocyte cells. Results Human express full-length P2×7A isoform. Treatment with lipopolysaccharide (LPS), potent inducer inflammation, significantly increased expression plasma membrane. Importantly, MED1101 internalisation already after 30 min incubation both physiological conditions presence stimulus (LPS) this was observable up 12 h its removal. Moreover, an impairment migration/transmigration through direct antagonism subsequent inhibition intracellular signal transduction processes Ca2+ influx MAPK phosphorylation. Conclusions Our results clearly demonstrate that acts induction down-stream pathways regulate migration/transmigration, thus playing potential role