Somatostatin down-regulates the expression and release of endozepines from cultured rat astrocytes via distinct receptor subtypes

Olfa Masmoudi, Pierrick Gandolfo, Tursonjan Tokay, Jérôme Leprince, Aurélia Ravni, Hubert Vaudry, Marie Christine Tonon

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Endozepines, a family of regulatory peptides related to diazepam-binding inhibitor (DBI), are synthesized and released by astroglial cells. Because rat astrocytes express various subtypes of somatostatin receptors (sst), we have investigated the effect of somatostatin on DBI mRNA level and endozepine secretion in rat astrocytes in secondary culture. Somatostatin reduced in a concentration-dependent manner the level of DBI mRNA in cultured astrocytes. This inhibitory effect was mimicked by the selective sst4 receptor agonist L803-087 but not by the selective sst1, sst2 and sst3 receptor agonists L779-591, L779-976 and L797-778, respectively. Somatostatin was unable to further reduce DBI mRNA level in the presence of the MEK inhibitor U0126. Somatostatin and the sst1, sst2 and sst4 receptor agonists induced a concentration-dependent inhibition of endozepine release. Somatostatin and the sst1, sst2 and sst4 receptor agonists also inhibited cAMP formation dose-dependently. In addition, somatostatin reduced forskolin-induced endozepine release. H89 mimicked the inhibitory effect of somatostatin on endozepine secretion. In contrast the PLC inhibitor U73122, the PKC activator PMA and the PKC inhibitor calphostin C had no effect on somatostatin-induced inhibition of endozepine release. The present data demonstrate that somatostatin reduces DBI mRNA level mainly through activation of sst4 receptors negatively coupled to the MAPK pathway, and inhibits endozepine release through activation of sst1, sst2 and sst4 receptors negatively coupled to the adenylyl cyclase/PKA pathway.

Original languageEnglish
Pages (from-to)561-571
Number of pages11
JournalJournal of Neurochemistry
Volume94
Issue number3
DOIs
Publication statusPublished - Aug 2005
Externally publishedYes

Fingerprint

Diazepam Binding Inhibitor
Somatostatin
Astrocytes
Rats
Down-Regulation
Somatostatin Receptors
Messenger RNA
Chemical activation
Mitogen-Activated Protein Kinase Kinases
Colforsin
Programmable logic controllers
Adenylyl Cyclases

Keywords

  • Astrocytes
  • Diazepam-binding inhibitor
  • Mitogen-activated protein kinase
  • Octadecaneuropeptide
  • Protein kinase A
  • Somatostatin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Somatostatin down-regulates the expression and release of endozepines from cultured rat astrocytes via distinct receptor subtypes. / Masmoudi, Olfa; Gandolfo, Pierrick; Tokay, Tursonjan; Leprince, Jérôme; Ravni, Aurélia; Vaudry, Hubert; Tonon, Marie Christine.

In: Journal of Neurochemistry, Vol. 94, No. 3, 08.2005, p. 561-571.

Research output: Contribution to journalArticle

Masmoudi, Olfa ; Gandolfo, Pierrick ; Tokay, Tursonjan ; Leprince, Jérôme ; Ravni, Aurélia ; Vaudry, Hubert ; Tonon, Marie Christine. / Somatostatin down-regulates the expression and release of endozepines from cultured rat astrocytes via distinct receptor subtypes. In: Journal of Neurochemistry. 2005 ; Vol. 94, No. 3. pp. 561-571.
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AU - Tokay, Tursonjan

AU - Leprince, Jérôme

AU - Ravni, Aurélia

AU - Vaudry, Hubert

AU - Tonon, Marie Christine

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