Pharmacological study of stem-cell-factor-induced mast cell histamine release with kinase inhibitors.
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 IC50 of 1.6 x 10(-5) M. Wortmannin, an inhibitor of phosphatidylinositol 3'-kinase (PI3 kinase), inhibited histamine release stimulated with SCF dose-dependently with IC50 of 4 x 10(-9) M. KT5926, an inhibitor of myosin light chain (MLC) kinase, reduced histamine release with IC50 of 1.8 x 10(-7) M. Staurosporine, an inhibitor of protein kinases, also inhibited SCF-induced histamine release with IC50 of 6.5 x 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.
Nagai
S
S
Department of Pediatrics, University of Teikyo School of Medicine, Tokyo, Japan.
Kitani
S
S
Hirai
K
K
Takaishi
T
T
Nakajima
K
K
Kihara
H
H
Nonomura
Y
Y
Ito
K
K
Morita
Y
Y
D000470:Alkaloids / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles; D019833:Genistein; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D007211:Indoles; D007529:Isoflavones / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine; D019089:Stem Cell Factor; D000077191:Wortmannin
D000470:Alkaloids; D000730:Androstadienes; D002227:Carbazoles; D016298:Hematopoietic Cell Growth Factors; D007211:Indoles; D007529:Isoflavones; D019089:Stem Cell Factor; C063769:KT 5926; D019833:Genistein; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019311:Staurosporine; D000077191:Wortmannin