Stimulation of Ca(2+)-dependent exocytosis and release of arachidonic acid in cultured mast cells (RBL-2H3) by quercetin

Basic secretagogues, such as compound 48/80, stimulate secretion in rat peritoneal mast cells by directly activating the heterotrimeric G-protein Gi(3) (Aridor M, et al. Science 1993;262:1569-72). Cultured RBL-2H3 mast cells do not normally respond to basic secretagogues, but acquire such responsiveness upon prolonged exposure to the kinase inhibitor, quercetin, which also increases the cellular level of Gi(3) (Senyshyn J, Baumgartner RA, Beaven MA. J Immunol 1998;160:5136-44). Expression of a GTPase-deficient mutant of Galphai(3) in RBL-2H3 cells results in the stimulation of Ca(2+)-triggered exocytosis and release of arachidonic acid (AA) (Zussman A, Hermuet S, Sagi-Eisenberg R. Eur J Biochem 1998;258:144-6). Here we show that long-term incubation with quercetin markedly stimulates Ca(2+)-triggered exocytosis and release of AA from the RBL-2H3 cells. We further show that membranes derived from such quercetin-treated cells display a reduced GTPase, but not ATPase, activity. Taken together with our previous observations, these results further implicate Gi(3) as one of the cellular targets through which quercetin confers responsiveness towards the family of basic secretagogues.