 | VIP, PACAP, AND RELATED PEPTIDES: THIRD INTERNATIONAL SYMPOSIUM
Copyright © 1998 by the New York Academy of Sciences
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Annals of the New York Academy of Sciences 865:141-146 (1998)
© 1998 New York Academy of Sciences
Pituitary Adenylate Cyclase Activating Polypeptide Induces Degranulation of Rat Peritoneal Mast Cells via High-Affinity PACAP Receptor-Independent Activation of G Proteins
JÖRG SEEBECKa,d,
MARIE-LUISE KRUSEb,
ANJONA SCHMIDT-CHOUDHURYc AND
WOLFGANG E. SCHMIDTb
aDepartment of Pharmacology, Christian-Albrechts University of Kiel, 24105 Kiel, Germany
cDepartment of Pediatrics, Christian-Albrechts University of Kiel, 24105 Kiel, Germany
bFirst Department of Internal Medicine, Christian-Albrechts University of Kiel, 24105 Kiel, Germany
dCorresponding author: Dr. Jörg Seebeck, Institut für Pharmakologie der CAU Kiel, Hospitalstr. 4, 24105 Germany; Tel.: 49-431-597-3508, Fax: 49-431-597-3522; E-mail: department{at}pharmakologie.uni-kiel.de
In this study, the secretory effects of PACAP and PACAP analogues on [ 3H]serotonin-loaded purified rat peritoneal mast cells (RPMCs) were investigated. PACAP(1-27) and PACAP(6-27) stimulated [ 3H]serotonin release with low potency (ED 50: 2 x 10 -6 M) but high efficacy. The N-terminally truncated PACAP form, PACAP(6-27), stimulated tracer release with an ED 50 of 0.2 x 10 -6 M, indicating a high-affinity PACAP receptor-independent mechanism of action. The secretory response to PACAP(1-27) could be inhibited by 60-min preincubation with pertussis toxin (ptx), which inhibits G proteins. U73122, a cell-permeable phospholipase C inhibitor, dose-dependently inhibited the secretory effect of 5 µM PACAP(1-27) with an IC 50 value of 4 µM ( N = 4; p > 0.006). We conclude that PACAP exerts a secretory effect in RPMCs by high-affinity PACAP receptor-independent direct activation of one or more G proteins, which may then activate the PLC-dependent signal-transduction pathway.
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