Inhibition of IgE-mediated histamine release by myosin light chain kinase inhibitors.
Wortmannin, a specific inhibitor of myosin light chain kinase (MLCK) blocked IgE mediated histamine release from rat basophilic leukemia cell (RBL-2H3) and human basophils dose-dependently. Its IC50 was 20 nM for RBL-2H3 cells and 30 nM for human basophils. There was complete inhibition at the concentration of 1 microM. Wortmannin inhibited partially the A23187 induced histamine release from RBL-2H3 cells (40% inhibition at 1 microM). This inhibition was not accompanied by any significant effect on cytosolic free calcium concentration [( Ca2+]i). KT5926, another MLCK inhibitor, inhibited histamine release comparably with wortmannin and blocked to some degree the increase of [Ca2+]i in RBL-2H3 cells. Thus, the phosphorylation of myosin seems to be involved in signal transduction through Fc epsilon RI.
Kitani
S
S
Department of Medicine and Physical Therapy, University of Tokyo School of Medicine, Japan.
Teshima
R
R
Morita
Y
Y
Ito
K
K
Matsuda
Y
Y
Nonomura
Y
Y
D000470:Alkaloids / Q000494:pharmacology*; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D001491:Basophils / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002227:Carbazoles; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D007211:Indoles; D015471:Leukemia, Basophilic, Acute / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors*; D051381:Rats; D014407:Tumor Cells, Cultured; D000077191:Wortmannin
D000470:Alkaloids; D000730:Androstadienes; D002227:Carbazoles; D007211:Indoles; C063769:KT 5926; D007073:Immunoglobulin E; D000001:Calcimycin; D009219:Myosin-Light-Chain Kinase; D002118:Calcium; D000077191:Wortmannin