The endozepine ODN stimulates [3H]thymidine incorporation in cultured rat astrocytes

被引：21

作者：

Gandolfo, P ^{[1
]}

Patte, C ^{[1
]}

Thoumas, JL ^{[1
]}

Leprince, J ^{[1
]}

Vaudry, H ^{[1
]}

Tonon, MC ^{[1
]}

机构：

[1] Univ Rouen, CNRS,INSERM,U143, European Inst Peptide Res IFRMP 23, Lab Cellular & Molec Neuroendocrinol, F-76821 Mont St Aignan, France

来源：

NEUROPHARMACOLOGY | 1999年 / 38卷 / 05期

关键词：

diazepam-binding inhibitor; octadecaneuropeptide; cell proliferation; central-type benzodiazepine receptors; gamma-aminobutyric acid; glial cells;

D O I：

10.1016/S0028-3908(98)00231-7

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

High concentrations of diazepam-binding inhibitor (DBI) mRNA have been detected in astrocytoma, suggesting that DBI-derived peptides may play a role in glial cell proliferation. In the present study, we have investigated the effect of a processing product of DBI, the octadecaneuropeptide ODN, on DNA synthesis in cultured rat astrocytes. At very low concentrations (10(-14) to 10(-11) M), ODN caused a dose-dependent increase of [H-3]thymidine incorporation. At higher doses (10(-10) to 10(-5) M), the effect of ODN gradually declined. The central-type benzodiazepine receptor antagonist flumazenil (10(-6) M) completely suppressed the stimulatory action of ODN whereas the peripheral-type benzodiazepine receptor ligand, PK11195 (10(-6) M) had no effect. The ODN-induced stimulation of [H-3]thymidine incorporation was mimicked by methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM). The GABA(A) receptor antagonist bicuculline (10(-4) M) suppressed the effect of both ODN and DMCM on DNA synthesis. Exposure of cultured astrocytes to the specific GABA(A) agonist 3APS (10(-10) to 10(-4) M) also induced a dose-related increase of [H-3]thymidine incorporation. The present study indicates that ODN, acting through central-type benzodiazepine receptors associated with the GABA(A) receptor complex, stimulates DNA synthesis in rat glial cells. These data provide evidence for an autocrine role of endozepines in the control of glial cell proliferation. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：725 / 732

页数：8

共 53 条

[1]

ALHO H, 1995, CELL GROWTH DIFFER, V6, P309

[2] IMMUNOHISTOCHEMISTRY OF DIAZEPAM BINDING INHIBITOR (DBI) IN THE CENTRAL-NERVOUS-SYSTEM AND PERIPHERAL ORGANS - ITS POSSIBLE ROLE AS AN ENDOGENOUS REGULATOR OF DIFFERENT TYPES OF BENZODIAZEPINE RECEPTORS [J].