SUBSTANCE P-RELATED INHIBITORS OF MAST-CELL EXOCYTOSIS ACT ON G-PROTEINS OR ON THE CELL-SURFACE

[p-Glu(5), D-Trp(7,9,10)]substance P-(5-11) inhibited mastoparan-stimu lated GTPase activity in homogenized rat peritoneal mast cells and dec reased histamine secretion induced by mastoparan from streptolysin O-p ermeabilized mast cells (IC50 of about 30 mu M), but not from intact c ells. In contrast, [D-Pro(4), D-Trp(7,9,10)]substance P-(4-11) inhibit ed the secretion from intact cells (IC(5)0 of about 10 mu M) but had n o effect on histamine secretion from permeabilized cells, suggesting t hat 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 p roteins. Pretreatment of mast cells with neuraminidase led to an inhib ition of the secretory response to mastoparan and related triggers. Th is response was restored following cell permeabilization, demonstratin g the role of the cell surface on the entry of mastoparan and related triggers and on their ability to reach G proteins sensitive to pertuss is toxin and [p-Glu(5), D-Trp(7,9,10)]substance P-(5-11). (C) 1998 Els evier Science B.V.