Stimulation of Ca2+-dependent exocytosis and release of arachidonic acid in cultured mast cells (RBL-2H3) by quercetin

Abstract

Basic secretagogues, such as compound 48/80, stimulate secretion in rat peritoneal mast cells by directly activating the heterotrimeric G-protein Gi₃ (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 Gi₃ (Senyshyn J, Baumgartner RA, Beaven MA. J Immunol 1998;160:5136–44). Expression of a GTPase-deficient mutant of Gαi₃ in RBL-2H3 cells results in the stimulation of Ca²⁺-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 Ca²⁺-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 Gi₃ as one of the cellular targets through which quercetin confers responsiveness towards the family of basic secretagogues.