It is well known that rat basophilic
leukemia cells (RBL-2H3) express high-affinity
IgE receptors (
Fc epsilon RI) and that the aggregation of these receptors causes the release of chemical mediators. When RBL-2H3 cells are sensitized with
IgE antibody and subsequently stimulated by an
antigen, significant histamine release and the
tyrosine phosphorylation of several
proteins are observed. In this study, we examined the effects of a synthetic
naphthalene derivative, (7E)-N-(2-carboxyphenyl)-8-(2-naphthyl)-5,6-trans-5,6-methano-7-++ +octenamide (TEI-6472), on the
Fc epsilon RI-mediated histamine release from RBL-2H3 cells. Preincubation for 10 min with 100 microM
TEI-6472 caused significant inhibition of
Fc epsilon RI-mediated histamine release from RBL-2H3 cells. Furthermore, Western blotting analysis using anti-
phosphotyrosine antibody showed that
Fc epsilon RI-mediated
tyrosine phosphorylation of 78 and 92 kDa
proteins in RBL-2H3 cells was also significantly inhibited.
Tyrosine phosphorylation of these 78 and 92 kDa
proteins was not induced by direct activation of
protein kinase C (PKC) by phorbol-12-myristate-13-acetate (PMA) and the
calcium ionophore A23187. However, the inhibition of histamine release from TEI-6472-treated RBL-2H3 cells was restored by direct activation of PKC. Taken together, these results suggest that
tyrosine phosphorylation of the 78 and 92 kDa
proteins in RBL-2H3 cells is involved in a signal transduction system for
histamine secretion, and that these
tyrosine phosphorylations may occur upstream of PKC activation.