Inhibition of growth factor-induced DNA synthesis in astrocytes by ligands of peripheral-type benzodiazepine receptors

Abstract

The effect of diazepam and specific ligands of peripheral-type benzodiazepine receptors (PBRs) on growth factor-induced DNA synthesis in quiescent cultures of rat astrocytes has been examined. It was found that diazepam inhibited the ability of basic fibroblast growth factor (bFGF) to stimulate [3H]thymidine incorporation; the IC50 was approximately 5 microM. Ro5-4864, a specific agonist of PBRs, also blocked bFGF-induced DNA synthesis. PK11195, which in some cases functions as an antagonist of PBRs, did not prevent the effect of Ro5-4864 on bFGF-induced DNA synthesis; rather, addition of PK11195 also inhibited bFGF-induced DNA synthesis. In addition, diazepam reduced the stimulation of DNA synthesis caused by epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), polypeptide growth factors coupled to receptor tyrosine kinases, as well as thrombin, an activator of G protein-coupled receptors. These data suggest that ligands of PBRs may limit astrocyte mitosis, a phenomenon that occurs following CNS injury.