title: Somatostatin down-regulates the expression and release of endozepines from cultured rat astrocytes via distinct receptor subtypes.
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.
authors: European Institute for Peptide Research (IFRMP 23), Laboratory of Cellular and Molecular Neuroendocrinology, INSERM U413, UA CNRS, University of Rouen, Mont-Saint-Aignan, France.
authors: Olfa
authors: O
authors: Masmoudi
authors: Pierrick
authors: P
authors: Gandolfo
authors: Tursonjan
authors: T
authors: Tokay
authors: Jérôme
authors: J
authors: Leprince
authors: Aurélia
authors: A
authors: Ravni
authors: Hubert
authors: H
authors: Vaudry
authors: Marie-Christine
authors: MC
authors: Tonon
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D015152:Blotting, Northern / Q000379:methods; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D026261:Diazepam Binding Inhibitor / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009479:Neuropeptides / Q000378:metabolism; D010446:Peptide Fragments; D010618:Phenanthrolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000819:agonists; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013004:Somatostatin / Q000819:agonists / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D026261:Diazepam Binding Inhibitor; D004791:Enzyme Inhibitors; D009479:Neuropeptides; D010446:Peptide Fragments; D010618:Phenanthrolines; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C067529:diazepam binding inhibitor (33-50); D005576:Colforsin; D013004:Somatostatin; D000242:Cyclic AMP