COOPERATION BETWEEN THE FC-EPSILON-R1 AND FORMYL PEPTIDE RECEPTOR SIGNALING PATHWAYS IN RBLFPR CELLS - THE CONTRIBUTION OF RECEPTOR-SPECIFIC CA2+ MOBILIZATION RESPONSES

RBLFPR mast cells express the tyrosine kinase-coupled IgE receptor, Fc eR1, and the G-protein-coupled formyl peptide receptor, FPR. FceR1 cro sslinking causes Ca2+ stores release, Ca2+ influx, Ins(1,4,5)P-3 produ ction and secretion. FPR ligation also mobilizes Ca2+, but without mea surable Ins(1,4,5)P-3 production or secretion. Co-stimulating the FPR and FceR1 induces more Ins(1,4,5)P-3 production and secretion than Fce R1 cross-linking alone. Costimulation also produces more rapid and sus tained Ca2+ responses than are generated by FceR1 activation alone. We identified multiple differences between the FPR- and FceR1-coupled Ca 2+ responses, including a more rapid Ca2+ spike response to FPR ligati on; intracellular Ca2+ stores that are empty following FceR1 crosslink ing but partially full following FPR activation; a more sustained Ca2 influx response to FceR1 crosslinking; and the immediate inhibition o f stimulated Ca2+ influx by FPR antagonists but not by monovalent liga nd that terminates FceR1 crosslinking. We hypothesize that the interac tion of receptor-specific Ca2+ mobilization pathways contributes to th e FPR-mediated potentiation of FceR1-coupled secretion. (C) 1997 Acade mic Press.