Effect of nonhydrolyzable guanosine phosphate on IgE-mediated activation of phospholipase C and histamine release from rodent mast cells

H. Saito, K. Ishizaka, T. Ishizaka

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Abstract

Rat mast cells and bone marrow-derived mouse mast cells (BMMC) were sensitized with mouse IgE mAb, and permeabilized by ATP to introduce guanosine-5'-O-(3-thiotriphosphate) (GTPγS) and/or guanosine-5'-O-(2-thiodiphosphate) (GDPβS) into the cells. After ATP-induced lesions were resealed with Mg2+, the cells were challenged by Ag to determine the effect of the nonhydrolyzable guanosine phosphate on Ag-induced hydrolysis of phosphoinositides and histamine release. Introduction of GTPγS into permeabilized rat mast cells or BMMC, followed by exposure of the cells to extracellular Ca2+, resulted in histamine release, but failed to induce hydrolysis of phosphoinositides. It was also found that introduction of GTPγS into the cells did not synergistically enhance Ag-induced histamine release. Introduction of GDPβS into sensitized BMMC inhibited the GTPγS-dependent, Ca2+-induced histamine release but failed to inhibit Ag-induced histamine release. The results suggest that GTPγS-dependent, Ca2+-induced histamine release and Ag-induced histamine release go through independent biochemical pathways. It was also found that introduction of GTPγS or GDPβS into sensitized BMMC neither enhanced nor inhibited Ag-induced formation of inositol phosphates. These results together with previous findings that pretreatment of BMMC with either pertussis toxin or cholera toxin does not affect Ag-induced hydrolysis or phosphoinositides, indicate that a G protein is involved in the transduction of IgE-mediated triggering signals to phospholipase C in rodent mast cells.

Original languageEnglish (US)
Pages (from-to)250-258
Number of pages9
JournalJournal of Immunology
Volume143
Issue number1
Publication statusPublished - 1989

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ASJC Scopus subject areas

  • Immunology

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