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

Joseph T. Neary, Svend L. Jorgensen, Allan M. Oracion, Jocelyn H. Bruce, Michael D. Norenberg

Research output: Contribution to journalArticle

34 Scopus citations

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 μM. 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.

Original languageEnglish (US)
Pages (from-to)27-30
Number of pages4
JournalBrain Research
Volume675
Issue number1-2
DOIs
StatePublished - Mar 27 1995

Keywords

  • Astrocyte
  • Basic fibroblast growth factor
  • Diazepam
  • DNA synthesis
  • Growth factor
  • Peripheral benzodiazepine receptor
  • Proliferation

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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