HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by MASMOUDI, O. Articles by TONON, M.-C. Search for Related Content PubMed PubMed Citation Articles by MASMOUDI, O. Articles by TONON, M.-C.

Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates endozepine release from cultured rat astrocytes via a PKA-dependent mechanism

European Institute for Peptide Research (IFRMP 23), Laboratory of Cellular and Molecular Neuroendocrinology, INSERM U413, UA CNRS, University of Rouen, 76821 Mont-Saint-Aignan, France; and
^* INRS-Institut Armand-Frappier, Université du Québec, Pointe-Claire, PQ, Canada H9R1G6

¹Correspondence: European Institute for Peptide Research (IFRMP 23), Laboratory of Cellular and Molecular Neuroendocrinology, INSERM U413, UA CNRS, University of Rouen, 76821 Mont-Saint-Aignan, France. E-mail: hubert.vaudry{at}univ-rouen.fr

Astroglial cells synthesize and release endozepines, neuropeptides that are related to the octadecaneuropeptide ODN. Glial cells also express PACAP/VIP receptors. We have investigated the possible effect of PACAP on the release of ODN-like immunoreactivity (ODN-LI) by cultured rat astrocytes. Administration of PACAP27 and PACAP38 induced a concentration-dependent increase in secretion of ODN-LI whereas VIP was 1000-fold less potent. The maximum effect of PACAP38 occurred after 5 min, then gradually declined during the next 10 min. The stimulatory effects of PACAP and VIP were abrogated by the PACAP antagonist PACAP6–38. PACAP38 stimulated cAMP formation, activated polyphosphoinositide turnover, and provoked calcium mobilization from IP₃-sensitive pools. The PKA inhibitor H89 suppressed PACAP-induced secretion of ODN-LI, whereas PLC inhibitor U73122 and the PKC inhibitor chelerythrine had no effect. In contrast, U73122 restored the stimulatory action of PACAP on ODN-LI release and cAMP formation during prolonged (15 min) incubation with the peptide, and this effect was prevented by PMA. The present results demonstrate that PACAP stimulates endozepine release through activation of PAC1 receptors coupled to the AC/PKA pathway. Our data also show that activation of the PLC/PKC pathway down-regulates the effect of PACAP on endozepine release.—Masmoudi, O., Gandolfo, P., Leprince, J., Vaudry, D., Fournier, A., Patte-Mensah, C., Vaudry, H., Tonon, M.-C. Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates endozepine release from cultured rat astrocytes via a PKA-dependent mechanism.

Key Words: endozepines • PAC1 receptor • PKA/PKC • intracellular Ca²⁺ • astroglial cells

This article has been cited by other articles:

				N. P.J. Brindle, P. Saharinen, and K. Alitalo Signaling and Functions of Angiopoietin-1 in Vascular Protection Circ. Res., April 28, 2006; 98(8): 1014 - 1023. [Abstract] [Full Text] [PDF]