The effect of a naphthalene derivative, TEI-6472, on histamine release and tyrosine phosphorylation in rat basophilic leukemia cells.
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.
Miyamoto
H
H
Department of Microbiology, Meiji College of Pharmacy, Tokyo, Japan.
Matsui
K
K
Arai
T
T
D000818:Animals; D001491:Basophils / Q000378:metabolism*; D002934:Cinnamates / Q000494:pharmacology; D004140:Dinitrophenols / Q000276:immunology; D006241:Haptens / Q000276:immunology; D006636:Histamine Release / Q000187:drug effects*; D015151:Immunoblotting; D007073:Immunoglobulin E / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015471:Leukemia, Basophilic, Acute; D009281:Naphthalenes / Q000494:pharmacology*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000276:immunology; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000276:immunology; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism; D012709:Serum Albumin / Q000276:immunology; D015398:Signal Transduction; D013440:Sulfides / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
D002934:Cinnamates; D004140:Dinitrophenols; D006241:Haptens; D007166:Immunosuppressive Agents; D009281:Naphthalenes; D010750:Phosphoproteins; D017455:Receptors, IgE; D012709:Serum Albumin; D013440:Sulfides; C058064:dinitrophenyl-human serum albumin conjugate; C060747:ST 638; C083345:TEI 6472; D019000:Phosphotyrosine; D007073:Immunoglobulin E; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C