Further studies on the structural requirements for polypeptide-mediated histamine release from rat mast cells.
Structure-activity studies have been performed on a series of naturally occurring and 'tailor-made' polypeptides, by measurement of ability to induce selective histamine release from normal rat peritoneal mast cells in vitro. Compounds investigated include corticotropin and melittin derivatives, mast-cell-degranulating peptide from bee venom, polymyxin B, bradykinin and various synthetic poly(amino acids) and short-chain peptides. It was confirmed that a cluster of four basic residues (lysine or arginine) was optimal for histamine release by corticotropin and melittin polypeptides, provided that the C-terminal carboxyl group was substituted (by, for instance, amidation). In contrast, the presence of a free C-terminal carboxyl group or nearby dicarboxylic acid residues led to a considerable diminution in histamine-releasing activity. Likewise, polypeptides comprised essentially of acidic amino acids were inactive. On the basis of these observations it has been possible to predict that synthetic peptides comprising a particular sequence within the Fc region of human immunoglobulin E, the immunoglobulin class particularly involved in mediation of allergic reactions of the immediate type, would possess potent histamine-releasing activity when similarly made to react with normal rat mast cells. The further study of such a structure should throw new light on the molecular basis of allergen-antibody triggering of mast cells.
D000324:Adrenocorticotropic Hormone; D000595:Amino Acid Sequence; D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D008555:Melitten; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D010455:Peptides; D008555:Melitten; D000324:Adrenocorticotropic Hormone