Beta-amyloid peptide stimulates endozepine release in cultured rat astrocytes through activation of N-formyl peptide receptors
✍ Scribed by Tursonjan Tokay; Raya Hachem; Olfa Masmoudi-Kouki; Pierrick Gandolfo; Laurence Desrues; Jerome Leprince; Helene Castel; Mickael Diallo; Mohamed Amri; Hubert Vaudry; Marie-Christine Tonon
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 365 KB
- Volume
- 56
- Category
- Article
- ISSN
- 0894-1491
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✦ Synopsis
Astroglial cells synthesize and release endozepines, a family of neuropeptides derived from diazepam-binding inhibitor (DBI). The authors have recently shown that b-amyloid peptide (Ab) stimulates DBI gene expression and endozepine release. The purpose of this study was to determine the mechanism of action of Ab in cultured rat astrocytes. Ab 25-35 and the N-formyl peptide receptor (FPR) agonist Nformyl-Met-Leu-Phe (fMLF) increased the secretion of endozepines in a dose-dependent manner with EC 50 value of 2 lM. The stimulatory effects of Ab 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, Ab 25-35 increased DBI mRNA expression through a FPR-independent mechanism. Ab 25-35 induced a transient stimulation of cAMP formation and a sustained activation of polyphosphoinositide turnover. The stimulatory effect of Ab 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 Ab 25-35 stimulates endozepine release from rat astrocytes through a FPR receptor positively coupled to PKA and PKC. V