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Pituitary adenylate cyclase‐activating polypeptide (PACAP) stimulates endozepine release from cultured rat astrocytes via a PKA‐dependent mechanism
Author(s) -
Masmoudi Olfa,
Gandolfo Pierrick,
Leprince Jerome,
Vaudry David,
Fournier Alain,
PatteMensah Christine,
Vaudry Hubert,
To MarieChristine
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0317com
Subject(s) - chelerythrine , protein kinase c , pituitary adenylate cyclase activating peptide , medicine , adenylate kinase , endocrinology , receptor , neuropeptide , vasoactive intestinal peptide , secretion , chemistry , second messenger system , antagonist , cyclase , signal transduction , biology , microbiology and biotechnology
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 IP 3 ‐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. FASEB J. 17, 17–27 (2003)