QUERCETIN SENSITIZES RBL-2H3 CELLS TO POLYBASIC MAST-CELL SECRETAGOGUES THROUGH INCREASED EXPRESSION OF GI GTP-BINDING PROTEINS LINKED TO APHOSPHOLIPASE-C SIGNALING PATHWAY

Polybasic secretagogues such as mastoparan, compound 48/80, substance P, and somatostatin stimulate secretion in rat peritoneal mast cells t hrough direct activation of the heterotrimeric G protein, G(i-3). Cult ured RBL-2H3 mast cells do not normally respond to these secretagogues , but, as reported here, they do so after prolonged exposure to the ki nase inhibitor, quercetin, This inhibitor, which causes phenotypic cha nges in RBL-2H3 cells, induces a substantial increase (more than seven fold) in the expression of ct subunits of the pertussis toxin-sensitiv e G proteins, G(i-2) and G(i-3). Compound 48/80-induced secretion is a ssociated with transient hydrolysis of phosphoinositides and a transie nt increase in cytosolic calcium ions. These responses are inhibited b y pertussis toxin, and in addition, secretion is blocked by calcium ch elation and the protein kinase C inhibitor, Ro31-7549, These results d elineate a pathway for compound 48/80-induced secretion in mast cells via G(i) protein(s), phospholipase C, calcium, and protein kinase C, T he results also imply that phospholipase C, most likely phospholipase C beta 3, can be transiently activated in RBL-2H3 cells by subunits of G(i) proteins to induce cellular responses.