title: PACAP stimulates biosynthesis and release of endozepines from rat astrocytes.
abstract: Astrocytes synthesize and release endozepines, a family of neuropeptides related to diazepam-binding inhibitor (DBI). Astroglial cells also express the receptors of pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP). In the present article, we show that PACAP dose dependently increases DBI gene expression and stimulates endozepine release through activation of PAC1-R. PACAP increases cAMP formation, enhances polyphosphoinositide turnover, and evokes calcium mobilization from intracellular Ca2+ pools. The effect of PACAP on endozepine release is mediated through the adenylyl cyclase/PKA pathway while the downregulation of astrocyte response to PACAP can be ascribed to activation of the PLC/PKC pathway.
authors.affiliation: Inserm U413, IFRMP 23, University of Rouen, 76821 Mont-Saint-Aignan, France.
authors.forename: Olfa
authors.initials: O
authors.lastname: Masmoudi-Kouki
authors.forename: Pierrick
authors.initials: P
authors.lastname: Gandolfo
authors.forename: Jerome
authors.initials: J
authors.lastname: Leprince
authors.forename: David
authors.initials: D
authors.lastname: Vaudry
authors.forename: Georges
authors.initials: G
authors.lastname: Pelletier
authors.forename: Alain
authors.initials: A
authors.lastname: Fournier
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Tonon
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D026261:Diazepam Binding Inhibitor / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D026261:Diazepam Binding Inhibitor; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases