mast-cell-degranulating-peptide and mastoparan

In the last decade, there has been renewed interest in biologically active peptides in fields like allergy, autoimmune diseases and antibiotic therapy. Mast cell degranulating peptides mimic G-protein receptors, showing different activity levels even among homologous peptides. Another important feature is their ability to interact directly with membrane phospholipids, in a fast and concentration-dependent way. The mechanism of action of peptide HR1 on model membranes was investigated comparatively to other mast cell degranulating peptides (Mastoparan, Eumenitin and Anoplin) to evidence the features that modulate their selectivity. Using vesicle leakage, single-channel recordings and zeta-potential measurements, we demonstrated that HR1 preferentially binds to anionic bilayers, accumulates, folds, and at very low concentrations, is able to insert and create membrane spanning ion-selective pores. We discuss the ion selectivity character of the pores based on the neutralization or screening of the peptides charges by the bilayer head group charges or dipoles.

Topics: Animals; Antimicrobial Cationic Peptides; Biophysical Phenomena; Cell Degranulation; Circular Dichroism; In Vitro Techniques; Intercellular Signaling Peptides and Proteins; Lipid Bilayers; Mast Cells; Membrane Potentials; Membranes, Artificial; Models, Molecular; Peptides; Protein Conformation; Rats; Rats, Wistar; Wasp Venoms

Venom sac extract of yellow jackets Vespula vulgaris was toxic in mice when injected intraperitoneally but not toxic when injected subcutaneously. Necropsy showed the toxicity to be an inflammatory response.. Venom peptide and protein fractions were tested to identify the inflammatory components. The active components were tested to establish whether they might function as adjuvant for venom protein-specific antibody response.. Venom toxicity required the synergistic action of two venom components, a mast cell degranulating peptide mastoparan and phospholipase A1. Both components stimulated prostaglandin E(2) release from murine peritoneal cells and macrophages. Mastoparan showed a weak activity to enhance IgE and IgG1 responses to a yellow jacket venom protein Ves v 5 in BALB/c mice. It was not possible to assess the adjuvant activity of phospholipase A1 because of its suppression of Ves v 5-specific response. Melittin, a mast cell degranulating peptide from bee venom, was inactive as an adjuvant for Ves v 5-specific response.. Yellow jacket venom contains two inflammatory components, mastoparan and phospholipase A1. Our findings suggest that mastoparan can function as a weak adjuvant for TH2 cell-associated antibody response.

Topics: Adjuvants, Immunologic; Animals; Antibody Formation; Antibody Specificity; Bee Venoms; Bees; Dinoprostone; Dose-Response Relationship, Immunologic; Immunoglobulin E; Immunoglobulin G; Inflammation Mediators; Intercellular Signaling Peptides and Proteins; Mice; Mice, Inbred BALB C; Models, Animal; Molecular Weight; Peptides; Phospholipases A; Phospholipases A1; Tumor Necrosis Factor-alpha; Wasp Venoms; Wasps

The molecular mechanism of action of several non-immunological histamine releasers has been investigated using pertussis toxin which interfers, via ADP-ribosylation, with some G-proteins. Pertussis toxin (100 ng/ml) inhibited histamine release induced by compound 48/80, substance P, mastoparan, peptide 401, bradykinin and spermine showing that a G-protein sensitive to pertussis toxin was involved in the non-immunological histamine release. All these compounds directly activate purified G-proteins. The sensitivity to pertussis toxin of this direct stimulatory effect was demonstrated for compound 48/80, mastoparan and substance P. Altogether these results suggest that a direct activation of G-protein might be the molecular mechanism of action of histamine secretagogues acting through a pertussis toxin sensitive G-protein and in this way mimic agonist-ligand receptor interaction.

Topics: Animals; Bradykinin; GTP-Binding Proteins; Histamine Release; Intercellular Signaling Peptides and Proteins; Male; Mast Cells; p-Methoxy-N-methylphenethylamine; Peptides; Pertussis Toxin; Rats; Rats, Inbred Strains; Spermine; Substance P; Virulence Factors, Bordetella; Wasp Venoms

In addition to wasp kinins, the wasp venom contains a series of hydrophobic peptides, mastoparans and chemotactic peptides as major peptidergic components. The first major component in the venom is mastoparam. The peptides in the mastoparan family are tetradecapeptide amides which cause degranulation of the mast cells to release histamine from the cells, and act on the adrenal chromaffin cells to release catecholamines and adenylic acids. Some mastoparans cause hemolysis and serotonin release from the platelets. The new cytotrophic peptides as the second major components are tridecapeptide amides possessing chemotactic activity for polymorphonuclear leucocytes and monocytes. Some of the peptides in this family also cause histamine release from the mast cells. Mastoparan takes a random coil structure in aqueous solution but changes its conformation to alpha-helix in methanolic solution or in the presence of lysophosphatidyl choline. This fact is confirmed also by the transferred nuclear overhauser effect by NMR analysis. The similar phenomenon was observed in the family of chemotactic peptides. The helical conformation of these peptides are amphipathic structure in which all of side chains of the hydrophobic amino acids are located on one side of the axis, and those of the basic or the hydrophilic amino acid residues are on an opposite side. Mastoparan enhances the membrane conductivity of the lipid bilayer when the peptide is investigated by the black lipid membrane experiment. This indicates that the peptide may be assembled in the membrane by changing its conformation and, for some reason, enhances the ion transfer through the membrane. These properties of the peptide may reveal various activities on the cell membrane.

Topics: Animals; Bee Venoms; Cell Membrane Permeability; Chemotactic Factors; Hymenoptera; Intercellular Signaling Peptides and Proteins; Kinins; Mast Cells; Peptides; Protein Conformation; Solubility; Wasp Venoms; Wasps