Mastoparan, a tetradecapeptide isolated from wasp venom, is known to not only induce the secretion of histamine but also cause cell lysis in rat peritoneal mast cells. This lytic effect makes investigations concerning MP-induced signaling mechanisms difficult. Here, we report that a mastoparan derivative peptide, [Lys(10), Leu(13)] mastoparan, also designated "mas 11", induces exocytosis with greater activity than mastoparan without the undesired lytic effect. The signaling mechanisms triggered by mas 11 were also investigated, and it was clearly demonstrated that mas 11 induced not only the non-lytic release of beta-hexosaminidase but also an increase in the concentration of cytosolic free Ca2+ in the cells and these effects were mostly prevented by pertussis toxin, suggesting the involvement of G(i)-type G protein in the signaling. Mas 11 is a promising stimulatory molecule with which to investigate the exocytotic mechanisms induced by not only mastoparan but also various amphiphilic peptides in the cells. (c) 2007 Elsevier Inc. All rights reserved.