Mastoparan causes cell permeabilisation and delayed activation of DNA synthesis in Swiss 3T3 fibroblasts

Mastoparan, a tetradecapeptide from wasp venom, preferentially activates the heterotrimeric G proteins, G(o) and G(i), by promoting GDP/GTP exchange. The peptide was originally identified as a potent secretagogue and has since been shown to promote DNA synthesis in Swiss 3T3 fibroblasts Here, we have shown that mastoparan (10-20 mu M), either alone or in combination with the co-mitogen insulin, had no effect on DNA synthesis when incubated with cells for 24 h. However, in the presence of insulin, the peptide evoked a small increase in DNA synthesis after incubation for 40 h Thus, unlike other mitogens, mastoparan caused a delayed activation of DNA synthesis. At concentrations of mastoparan (15-17.5 mu M) which promoted DNA synthesis, the peptide caused a rapid release of lactate dehydrogenase from the cells. These data suggest that the mitogenic action of mastoparan occurs by a mechanism distinct from that of physiological mitogens. Copyright (C) 1996 Elsevier Science Inc.