Mast cells are stimulated to release histamine via nonspecific ligand binding ("peptidergic release") by various peptides, including purified peptides, peptide analogs, mononuclear cell supernatants and venom peptides. Most of this reaction is suppressed with near physiological levels of extracellular Ca++. A complex naturally occurring pool of small proteins/peptides known to cause inflammatory events, venom peptides of C. v. helleri, was used as a model to better understand the overall significance of this reaction. Significant inhibition was seen at 1 mM and was level at 5-20 mM Ca++, with 5 mM Ca++ inhibiting 90% of the reaction. Pertussis toxin maximally inhibited 95% of the reaction in a biphasic response. Inhibition was dependent on the dose of venom toxins used. Increased levels of venom did not abrogate the inhibition by Ca++. The reaction was 80% completed in 2 min., and virtually complete at 5 minutes. These findings indicate that venom, historically a source of pharmacologically active peptides, behaves similarly to other peptide agonists for mast cells and provided new useful data on responses at high agonist concentrations; and is a benchmark for planning the discovery of novel agonists while assayed under conditions of agonist excess while suppressing the nonspecific peptidergic responses.
|State||Published - 20 Mar 1998|