title: Influence of alpha-helicity, amphipathicity and D-amino acid incorporation on the peptide-induced mast cell activation.
abstract: Mast cell activation by polycationic substances is believed to result from a direct activation of G protein alpha subunits and it was suggested that the adaption of amphipathic, alpha-helical conformations would allow the peptide to reach the cytosolic compartment to interact with G proteins (Mousli et al., 194, Immunopharmacology 27, 1, for review). We investigated the histamine-releasing activity of model peptides as well as analogues of magainin 2 amide and neuropeptide Y with different amphipathicities and alpha-helix content on rat peritoneal mast cells. Amphipathic helicity is not a prerequisite for mast cell activation. Moreover, non-helical magainin peptides with high histamine-releasing activity were less active in the liberation of carboxyfluoresceine from negatively charged liposomes, indicating that peptide-induced mast cell activation and peptide-induced membrane perturbation do not correlate. In contrast to the negligible influence of the secondary structure, amino acid configuration may exert a striking influence on peptide-induced mast cell activation. Thus histamine-release by substance P was markedly impaired when the L-amino acids in the positively charged N-terminal region were replaced by D-amino acids, with [D-Arg1)substance P being the most inactive substance P diastreoisomer.
authors.affiliation: Department of Clinical Biochemistry, Queen's University of Belfast, Northern Ireland, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Cross
authors.forename: M
authors.initials: M
authors.lastname: Ennis
authors.forename: E
authors.initials: E
authors.lastname: Krause
authors.forename: M
authors.initials: M
authors.lastname: Dathe
authors.forename: D
authors.initials: D
authors.lastname: Lorenz
authors.forename: G
authors.initials: G
authors.lastname: Krause
authors.forename: M
authors.initials: M
authors.lastname: Beyermann
authors.forename: M
authors.initials: M
authors.lastname: Bienert
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D006636:Histamine Release / Q000187:drug effects*; D008081:Liposomes; D054806:Magainins; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D009478:Neuropeptide Y / Q000031:analogs & derivatives* / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D017433:Protein Structure, Secondary; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D029867:Xenopus Proteins
chemical_list: D023181:Antimicrobial Cationic Peptides; D008081:Liposomes; D054806:Magainins; D009478:Neuropeptide Y; D010455:Peptides; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; D013373:Substance P