Substance P-related inhibitors of mast cell exocytosis act on G-proteins or on the cell surface

European Journal of Pharmacology
A ChahdiY Landry

Abstract

[p-Glu5,D-Trp(7,9,10)]substance P-(5-11) inhibited mastoparan-stimulated GTPase activity in homogenized rat peritoneal mast cells and decreased histamine secretion induced by mastoparan from streptolysin O-permeabilized mast cells (IC50 of about 30 microM), but not from intact cells. In contrast, [D-Pro4,D-Trp(7,9,10)]substance P-(4-11) inhibited the secretion from intact cells (IC50 of about 10 microM) but had no effect on histamine secretion from permeabilized cells, suggesting that this peptide exerts its inhibitory effect on the plasma membrane, whereas [p-Glu5,D-Trp(7,9,10)]substance P-(5-11) interacts with G proteins. Pretreatment of mast cells with neuraminidase led to an inhibition of the secretory response to mastoparan and related triggers. This response was restored following cell permeabilization, demonstrating the role of the cell surface on the entry of mastoparan and related triggers and on their ability to reach G proteins sensitive to pertussis toxin and [p-Glu5,D-Trp(7,9,10)]substance P-(5-11).

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Citations

Jan 16, 2002·European Journal of Pharmacology·Xavier Ferry, Yves Landry
Dec 18, 2012·Gut·Sjoerd H W van BreeGianluca Matteoli
Mar 19, 2016·Canadian Journal of Physiology and Pharmacology·Honghua JinPengyuan Sun
Apr 17, 2004·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·S C BischoffM Schemann
Oct 10, 2007·Immunology·Marianna KulkaRobert P Schleimer

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