Histamine Release Induced by Proteolytic Digests of Human Serum Albumin: Isolation and Structure of an Active Peptide from Pepsin Treatment

Abstract

Treatment of human serum albumin with a proteolytic enzyme such as pepsin, α-chymotrypsin, cathepsin D or trypsin generated histamine releasing peptides. A low-molecular weight peptide (P-1) responsible for releasing histamine was isolated from peptic digests of human serum albumin by affinity chromatography on heparin-Ultrogel and reversed-phase high performance liquid chromatography. The amino acid sequence of the P-1 was estimated to be V-R-Y-T-K-K-V-P-Q-V-S-T-P-T-L by Edman degradation. The sequence determined appears to correspond to residues 409-423 of human serum albumin. Peptide P-1 produced dose-related histamine release from isolated rat mast cells in the concentration range of 1-50 μM. The intradermal injection of the P-1 (0.5 μg) increased capillary permeability in rats. This response was blocked by the antihistamine diphenhydramine.