PACAP stimulates biosynthesis and release of endozepines from rat astrocytes.
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.
Masmoudi-Kouki
Olfa
O
Inserm U413, IFRMP 23, University of Rouen, 76821 Mont-Saint-Aignan, France.
Gandolfo
Pierrick
P
Leprince
Jerome
J
Vaudry
David
D
Pelletier
Georges
G
Fournier
Alain
A
Vaudry
Hubert
H
Tonon
Marie-Christine
MC
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
D026261:Diazepam Binding Inhibitor; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases