Parabutoporin (PP) and opistoporin 1 (OP1) are amphipathic alpha-helical antimicrobial peptides that were recently isolated from scorpion venom. In assays in which single granulocyte-like HL-60 cells as well as cells in suspension were used, both peptides were able to induce a reversible Ca2+ release from intracellular stores and to increase Ca2+ influx. Both effects could be clearly differentiated for OP1, inducing Ca2+ release at lower concentrations. The Ca2+ release was pertussis toxin-sensitive indicating the involvement of G-proteins. Ca2+ release depended on the stage of differentiation of the cells with undifferentiated cells being the most sensitive. Desensitization occurred with OP1. No cross-desensitization occurred between OP1 and the bacterial chemoattractant fMLP indicating the involvement of different types of receptors. Ca2+ release by OP1 was found not to be mediated via interaction with the formyl peptide receptor-like 1. Although some of the results might favor a receptor-like interaction, the receptor involved could not be identified. (C) 2003 Elsevier Inc. All rights reserved.