PACAP Stimulates Biosynthesis and Release of Endozepines from Rat Astrocytes

Olfa Masmoudi-Kouki (1, 2, 3) , Pierrick Gandolfo (2, 3) , Jérôme Leprince (2, 3) , David Vaudry (2, 3) , Georges Pelletier (4) , Alain Fournier (5) , Hubert Vaudry (2, 3) , Marie-Christine Tonon (2, 3)

1 University of Tunis - Faculty of Sciences of Tunis
2 Neuroendocrinologie cellulaire et moléculaire
3 IFRMP 23 - Institut Fédératif de Recherches Multidisciplinaires sur les Peptides
4 Laval University Medical center
5 INRS-IAF - Institut Armand Frappier

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.

Domaines: Chimie thérapeutique; Interactions cellulaires [q-bio.CB]; Neurobiologie; Pharmacologie

Olfa Masmoudi-Kouki, Pierrick Gandolfo, Jérôme Leprince, David Vaudry, Georges Pelletier, et al.. PACAP Stimulates Biosynthesis and Release of Endozepines from Rat Astrocytes. Annals of the New York Academy of Sciences, 2006, 1070 (1), pp.411-416. ⟨10.1196/annals.1317.094⟩. ⟨hal-01973027⟩