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

doi:10.1016/0006-8993(95)00031-K

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

Pathology

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Pages (from-to)	27-30
Number of pages	4
Journal	Brain research
Volume	675
Issue number	1-2
DOIs	https://doi.org/10.1016/0006-8993(95)00031-K
State	Published - 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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title = "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 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.",

keywords = "Astrocyte, Basic fibroblast growth factor, Diazepam, DNA synthesis, Growth factor, Peripheral benzodiazepine receptor, Proliferation",

author = "Neary, {Joseph T.} and Jorgensen, {Svend L.} and Oracion, {Allan M.} and Bruce, {Jocelyn H.} and Norenberg, {Michael D.}",

note = "Funding Information: We are grateful to Janina Blicharska, Lin Kong, and Wenying Zhao for their expert technical assistance, and to Dr. Judith Abraham, Scios, Inc., for providing bFGF. This work was supported by Department of Veterans Affairs, the National Institutes of Health (NS30291, DK38153, NS26887), and the Geriatric Research, Education and Clinical Centers.",

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language = "English (US)",

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AU - Neary, Joseph T.

AU - Jorgensen, Svend L.

AU - Oracion, Allan M.

AU - Bruce, Jocelyn H.

AU - Norenberg, Michael D.

N1 - Funding Information: We are grateful to Janina Blicharska, Lin Kong, and Wenying Zhao for their expert technical assistance, and to Dr. Judith Abraham, Scios, Inc., for providing bFGF. This work was supported by Department of Veterans Affairs, the National Institutes of Health (NS30291, DK38153, NS26887), and the Geriatric Research, Education and Clinical Centers.

PY - 1995/3/27

Y1 - 1995/3/27

N2 - 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.

AB - 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.

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KW - Basic fibroblast growth factor

KW - Diazepam

KW - DNA synthesis

KW - Growth factor

KW - Peripheral benzodiazepine receptor

KW - Proliferation

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

Abstract

Keywords

ASJC Scopus subject areas

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