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Ann N Y Acad Sci. 1998 Dec 11;865:141-6.

Pituitary adenylate cyclase activating polypeptide induces degranulation of rat peritoneal mast cells via high-affinity PACAP receptor-independent activation of G proteins.

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1
Department of Pharmacology, Christian-Albrechts University of Kiel, Germany. department@pharmakologie.uni-kiel.de

Abstract

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 microM PACAP(1-27) with an IC50 value of 4 microM (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.

[Indexed for MEDLINE]

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