Interaction of Benzodiazepines with Mouse Macrophages

Mouse peritoneal inflammatory macrophages have a saturable binding site for [3H]flunitrazepam with a KD of 43 +/- 7 nM and Bmax of 391 +/- 58 fmol per 10(6) cells, which corresponds to 250 000 sites per cell. The IC50 values for PK 11195, Ro 5-4864, diazepam, flunitrazepam, clonazepam, ethyl-beta carboline 3-carboxylate and Ro 15-1788 were 5.6, 6.5, 21, 40, 3 000, 12 000 and 80 000 nM respectively; gamma-aminobutyric acid did not displace [3H]flunitrazepam. These results indicate that the benzodiazepine binding site on the macrophage is of the peripheral type. In vivo experiments show that, at 1 mg/kg, peripheral and mixed type molecules stimulate the humoral response to sheep red blood cells while central type benzodiazepines are inactive. The hypothesis that this effect is mediated through the binding on the macrophage may be considered.