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The stimulatory effect of the octadecaneuropeptide (ODN) on cytosolic Ca2+ in rat astrocytes is not mediated through classical benzodiazepine receptors.

Abstract : Diazepam-binding inhibitor has been initially isolated from the rat brain from its ability to compete with benzodiazepines for their receptors. We have recently shown that the octadecaneuropeptide (diazepam-binding inhibitor-(33-50) or ODN) induces an increase in cytosolic free Ca2+ concentration ([Ca2+]i) in astroglial cells. The purpose of the present study was to determine whether central-type benzodiazepine receptors or peripheral-type benzodiazepine receptors are involved in the response of cultured rat astrocytes to ODN. The mixed central-/peripheral-type benzodiazepine receptor ligand flunitrazepam (10(-10) to 10(-6) M), the specific peripheral-type benzodiazepine receptor agonist Ro5-4864 (10(-10) to 10(-6) M) and the peripheral-type benzodiazepine receptor 'antagonist' PK 11195 (10(-9) to 10(-6) M) all induced a dose-dependent increase in [Ca2+]i. At high doses (10(-7) to 10(-5) M), the central-type benzodiazepine receptor agonist clonazepam also mimicked the stimulatory effect of ODN on [Ca2+]i. However, the [Ca2+]i rise induced by ODN was blocked neither by PK 11195 nor by the central-type benzodiazepine receptor antagonist flumazenil (10(-6) M each). Binding of [3H]flunitrazepam to intact astrocytes was displaced by low concentrations of the peripheral-type benzodiazepine receptor ligands flunitrazepam, Ro5 4864 and PK 11195, and by high concentrations of clonazepam. In contrast, ODN did not compete for [3H]flunitrazepam binding in intact cells. These data indicate that the effect of ODN on Ca2+ mobilization in rat astrocytes is mediated by high affinity receptors which are not related to classical benzodiazepine receptors.
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https://hal-normandie-univ.archives-ouvertes.fr/hal-01962733
Contributor : Jérôme Leprince <>
Submitted on : Thursday, December 20, 2018 - 6:11:22 PM
Last modification on : Tuesday, April 7, 2020 - 3:36:04 PM

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  • HAL Id : hal-01962733, version 1
  • PUBMED : 9098698

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M Gandolfo, C. Patte, Jérôme Leprince, J Thoumas, H. Vaudry, et al.. The stimulatory effect of the octadecaneuropeptide (ODN) on cytosolic Ca2+ in rat astrocytes is not mediated through classical benzodiazepine receptors.. European Journal of Pharmacology, Elsevier, 1997, 322 (2-3), pp.275-81. ⟨hal-01962733⟩

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