Influence of alpha-helicity, amphipathicity and D-amino acid incorporation on the peptide-induced mast cell activation

L.J.M. Cross, Madeleine Ennis, E. Krause, M. Dathe, D. Lorenz, G. Krause, M. Beyermann, M. Bienert

Research output: Contribution to journalArticle

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., 1994, 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-Arg(1)]substance P being the most inactive substance P diastereoisomer.
Original languageEnglish
Pages (from-to)291-300
Number of pages10
JournalEUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION
Volume291
Publication statusPublished - 1995

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    Cross, L. J. M., Ennis, M., Krause, E., Dathe, M., Lorenz, D., Krause, G., Beyermann, M., & Bienert, M. (1995). Influence of alpha-helicity, amphipathicity and D-amino acid incorporation on the peptide-induced mast cell activation. EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 291, 291-300.