肌球蛋白轻链激酶抑制剂对IgE介导的组胺释放的抑制作用

Inhibition of IgE-mediated histamine release by myosin light chain kinase inhibitors.

作者信息

Kitani S, Teshima R, Morita Y, Ito K, Matsuda Y, Nonomura Y

机构信息

Department of Medicine and Physical Therapy, University of Tokyo School of Medicine, Japan.

出版信息

Biochem Biophys Res Commun. 1992 Feb 28;183(1):48-54. doi: 10.1016/0006-291x(92)91607-r.

DOI:10.1016/0006-291x(92)91607-r

PMID:1371921

Abstract

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.

摘要

渥曼青霉素，一种肌球蛋白轻链激酶（MLCK）的特异性抑制剂，可剂量依赖性地阻断IgE介导的大鼠嗜碱性白血病细胞（RBL - 2H3）和人嗜碱性粒细胞释放组胺。其对RBL - 2H3细胞的IC50为20 nM，对人嗜碱性粒细胞为30 nM。在1 microM的浓度下有完全抑制作用。渥曼青霉素部分抑制了A23187诱导的RBL - 2H3细胞组胺释放（在1 microM时抑制40%）。这种抑制并未伴随对胞质游离钙浓度[Ca2+]i的任何显著影响。另一种MLCK抑制剂KT5926与渥曼青霉素类似地抑制组胺释放，并在一定程度上阻断了RBL - 2H3细胞中[Ca2+]i的升高。因此，肌球蛋白的磷酸化似乎参与了通过FcεRI的信号转导。