Edited by Luke O'Neillrelease, which was shown to be temperature-dependent and sensitive to bafilomycin A 1 and tetanus toxin, was significantly suppressed by VPAT gene RNA interference. Under these conditions, expression of vesicular monoamine transporter 2 was unaffected, but antigen-dependent histamine release was significantly suppressed, which was recovered by the addition of 1 mM spermine. These results strongly suggest that VPAT is expressed and is responsible for vesicular storage of spermine and spermidine in novel secretory granules that differ from histamine-and serotonin-containing granules and is involved in vesicular release of these polyamines from mast cells.