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.
Department of Medicine and Physical Therapy, University of Tokyo School of Medicine, Japan.
S
S
Kitani
R
R
Teshima
Y
Y
Morita
K
K
Ito
Y
Y
Matsuda
Y
Y
Nonomura
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