Peripheral benzodiazepines enhance the respiratory burst of macrophage-like P388D1 cells stimulated by arachidonic acid.
P388D1, a murine cell with macrophage properties, responds to exogenous arachidonic acid with superoxide anion production. This oxidative burst is enhanced by peripheral and mixed type benzodiazepines and this stimulation is specifically reversed by the peripheral antagonist PK 11195. In contrast, PK 11195 is unable to antagonize a stimulation caused by a non-benzodiazepine ligand such as the chemotactic peptide fMet-Leu-Phe. The optimal concentrations were close to 10 nM and corresponded to the affinities of the compounds for the peripheral benzodiazepine receptor detected on these cells. Compared to other tissues where peripheral benzodiazepines acted only at micromolar concentrations, the macrophage with its functional receptor appears as a privileged site of action for these molecules.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D002998:Clonazepam / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D007546:Isoquinolines / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D001095:Arachidonic Acids; D001570:Benzodiazepinones; D007546:Isoquinolines; D011963:Receptors, GABA-A; D013481:Superoxides; D016718:Arachidonic Acid; C028513:4'-chlorodiazepam; D002998:Clonazepam; D003975:Diazepam; C037850:PK 11195