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

Eur J Pharmacol. 1998 Jan 12;341(2-3):329-35. doi: 10.1016/s0014-2999(97)01480-5.


[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).

MeSH terms

  • Animals
  • Bacterial Proteins
  • Exocytosis / drug effects*
  • GTP Phosphohydrolases / drug effects
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Proteins / antagonists & inhibitors
  • GTP-Binding Proteins / drug effects*
  • Histamine Release / drug effects*
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Mast Cells / drug effects*
  • Mast Cells / metabolism
  • Neuraminidase / pharmacology
  • Peptide Fragments / pharmacology*
  • Peptides / pharmacology
  • Permeability
  • Rats
  • Rats, Wistar
  • Streptolysins / pharmacology
  • Substance P / analogs & derivatives*
  • Substance P / pharmacology
  • Wasp Venoms / pharmacology


  • Bacterial Proteins
  • Intercellular Signaling Peptides and Proteins
  • Peptide Fragments
  • Peptides
  • Streptolysins
  • Wasp Venoms
  • streptolysin O
  • Substance P
  • mastoparan
  • substance P (4-11), Pro(4)-Trp(7,9,10)-
  • Neuraminidase
  • GTP Phosphohydrolases
  • GTP-Binding Proteins