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Pituitary Adenylate Cyclase Activating Polypeptide Induces Degranulation of Rat Peritoneal Mast Cells via High‐Affinity PACAP Receptor‐Independent Activation of G Proteins
Author(s) -
SEEBECK JÖRG,
KRUSE MARIELUISE,
SCHMIDTCHOUDHURY ANJONA,
SCHMIDT WOLFGANG E.
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb11172.x
Subject(s) - degranulation , pertussis toxin , receptor , adenylate kinase , phospholipase c , medicine , cyclase , endocrinology , pituitary adenylate cyclase activating peptide , mast cell , signal transduction , chemistry , biology , g protein , microbiology and biotechnology , neuropeptide , biochemistry , vasoactive intestinal peptide , immunology
A bstract : In this study, the secretory effects of PACAP and PACAP analogues on [ 3 H]serotonin‐loaded purified rat peritoneal mast cells (RPMCs) were investigated. PACAP(1‐27) and PACAP(6‐27) stimulated [ 3 H]serotonin release with low potency (ED 50 : 2 × 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 × 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.