1. Beta-amyloid peptide stimulates endozepine release in cultured rat astrocytes through activation ofN-formyl peptide receptors
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Hélène Castel, Tursonjan Tokay, Mohamed Amri, Pierrick Gandolfo, Marie Christine Tonon, Hubert Vaudry, Olfa Masmoudi-Kouki, Raya Hachem, Jérôme Leprince, Mickaël Diallo, Laurence Desrues, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (IFRMP 23), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Faculté des Sciences Mathématiques, Physiques et Naturelles de Tunis (FST), and Université de Tunis El Manar (UTM)
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[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,MESH: Receptors, Formyl Peptide ,[CHIM.THER]Chemical Sciences/Medicinal Chemistry ,MESH: Neuropeptides ,Adenylyl cyclase ,chemistry.chemical_compound ,0302 clinical medicine ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,MESH: Animals ,MESH: Peptide Fragments ,Receptor ,Cells, Cultured ,Protein Kinase C ,Diazepam Binding Inhibitor ,0303 health sciences ,MESH: Amyloid beta-Peptides ,Cell biology ,Neurology ,medicine.symptom ,MESH: Cells, Cultured ,Endozepine ,MESH: Rats ,MESH: Receptor Cross-Talk ,MESH: Cyclic AMP-Dependent Protein Kinases ,Biology ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,mental disorders ,medicine ,Animals ,Rats, Wistar ,Protein kinase A ,Protein kinase C ,030304 developmental biology ,Amyloid beta-Peptides ,Phospholipase C ,Neuropeptides ,MESH: Rats, Wistar ,Receptor Cross-Talk ,MESH: Protein Kinase C ,Cyclic AMP-Dependent Protein Kinases ,Receptors, Formyl Peptide ,Molecular biology ,Peptide Fragments ,Rats ,MESH: Astrocytes ,Chelerythrine ,Mechanism of action ,chemistry ,Astrocytes ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,MESH: Diazepam Binding Inhibitor ,030217 neurology & neurosurgery - Abstract
International audience; Astroglial cells synthesize and release endozepines, a family of neuropeptides derived from diazepam-binding inhibitor (DBI). The authors have recently shown that beta-amyloid peptide (Abeta) stimulates DBI gene expression and endozepine release. The purpose of this study was to determine the mechanism of action of Abeta in cultured rat astrocytes. Abeta(25-35) and the N-formyl peptide receptor (FPR) agonist N-formyl-Met-Leu-Phe (fMLF) increased the secretion of endozepines in a dose-dependent manner with EC(50) value of approximately 2 microM. The stimulatory effects of Abeta(25-35) and the FPR agonists fMLF and N-formyl-Met-Met-Met (fMMM) on endozepine release were abrogated by the FPR antagonist N-t-Boc-Phe-Leu-Phe-Leu-Phe. In contrast, Abeta(25-35) increased DBI mRNA expression through a FPR-independent mechanism. Abeta(25-35) induced a transient stimulation of cAMP formation and a sustained activation of polyphosphoinositide turnover. The stimulatory effect of Abeta(25-35) on endozepine release was blocked by the adenylyl cyclase inhibitor somatostatin, the protein kinase A (PKA) inhibitor H89, the phospholipase C inhibitor U73122, the protein kinase C (PKC) inhibitor chelerythrine and the ATP binding cassette transporter blocker glyburide. Taken together, these data demonstrate for the first time that Abeta(25-35) stimulates endozepine release from rat astrocytes through a FPR receptor positively coupled to PKA and PKC.
- Published
- 2008
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