Pharmacological study of stem-cell-factor-induced mast cell histamine release with kinase inhibitors
| Autor: | Koichi Hirai, Hidetoshi Kihara, Kazunori Nakajima, Yutaka Morita, Koji Ito, Toshiaki Takaishi, Seiichi Kitani, S. Nagai, Yoshiaki Nonomura |
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| Rok vydání: | 1995 |
| Předmět: |
Indoles
Biophysics Carbazoles Mitogen-activated protein kinase kinase Pharmacology In Vitro Techniques Hematopoietic Cell Growth Factors Biochemistry Histamine Release MAP2K7 Wortmannin Rats Sprague-Dawley chemistry.chemical_compound Phosphatidylinositol 3-Kinases Alkaloids Histamine H2 receptor Animals ASK1 Mast Cells Molecular Biology Protein Kinase C Stem Cell Factor biology MAP kinase kinase kinase Cyclin-dependent kinase 2 Cell Biology Protein-Tyrosine Kinases Staurosporine Genistein Isoflavones Cell biology Rats Androstadienes Phosphotransferases (Alcohol Group Acceptor) chemistry biology.protein Cyclin-dependent kinase 9 Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 208(2) |
| ISSN: | 0006-291X |
| Popis: | Stem cell factor (SCF) is a ligand for c-kit receptor and has a critical role in the development of mast cells. In this study, we investigated the effect of a panel of kinase inhibitors on SCF-induced histamine release from rat peritoneal mast cells. Genistein, an inhibitor of tyrosine kinases, inhibited SCF-induced histamine release with IC 50 of 1.6 × 10 -5 M. Wortmannin, an inhibitor of phosphatidylinositol 3′-kinase (PI3 kinase), inhibited histamine release stimulated with SCF dose-dependently with IC 50 of 4 × 10 −9 M. KT5926, an inhibitor of myosin light chain (MLC) kinase, reduced histamine release with IC 50 of 1.8 × 10 −7 M. Staurosporine, an inhibitor of protein kinases, also inhibited SCF-induced histamine release with IC 50 of 6.5 × 10 −8 M. These results show the early involvement of tyrosine kinase and PI3 kinase and the possible role of MLC kinase in the late secretory phase in the signaling pathway used by SCF. |
| Databáze: | OpenAIRE |
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