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

Abstract

[ p-Glu 5, 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 (IC 50 of about 30 μM), but not from intact cells. In contrast, [ d-Pro 4, d-Trp 7,9,10]substance P-(4–11) inhibited the secretion from intact cells (IC 50 of about 10 μM) but had no effect on histamine secretion from permeabilized cells, suggesting that this peptide exerts its inhibitory effect on the plasma membrane, whereas [ p-Glu 5, 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-Glu 5, d-Trp 7,9,10]substance P-(5–11).