INHIBITION OF GROWTH FACTOR-INDUCED DNA-SYNTHESIS IN ASTROCYTES BY LIGANDS OF PERIPHERAL-TYPE BENZODIAZEPINE RECEPTORS

The effect of diazepam and specific ligands of peripheral-type benzodi azepine receptors (PBRs) on growth factor-induced DNA synthesis in qui escent cultures of rat astrocytes has been examined. It was found that diazepam inhibited the ability of basic fibroblast growth factor (bFG F) to stimulate [H-3]thymidine incorporation; the IC50 was approximate ly 5 mu M. Ro5-4864, a specific agonist of PBRs, also blocked bFGF-ind uced DNA synthesis. PK11195, which in some cases functions as an antag onist 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 s ynthesis caused by epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), polypeptide growth factors coupled to receptor t yrosine kinases, as well as thrombin, an activator of G protein-couple d receptors. These data suggest that ligands of PBRs may limit astrocy te mitosis, a phenomenon that occurs following CNS injury.