Pituitary Adenylate Cyclase Activating Polypeptide Induces Degranulation of Rat Peritoneal Mast Cells via High-Affinity PACAP Receptor-Independent Activation of G Proteins.
SEEBECK, JORG a,d; KRUSE, MARIE-LUISE b; SCHMIDT-CHOUDHURY, ANJONA c; SCHMIDT, WOLFGANG E. b
[Report] Annals of the New York Academy of Sciences. 865:141-146, 1998.

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colon; 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 (ED50: 2 x 10-6 M) but high efficacy. The N-terminally truncated PACAP form, PACAP(6-27), stimulated tracer release with an ED50 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 [mu]M PACAP(1-27) with an IC50 value of 4 [mu]M (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.

Copyright 1998 by the New York Academy of Sciences. All rights reserved.