Morita Y, Takaishi T, Honda Z, Miyamoto T
Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Japan.
Allergy. 1988 Feb;43(2):100-4. doi: 10.1111/j.1398-9995.1988.tb00401.x.
In this study, we investigated the role of calcium and phospholipid-dependent protein kinase (protein kinase C, PKC) in the modulation of histamine release from human basophils. A novel and potent inhibitor of PKC, K-252a, inhibited the release of histamine induced by anti-IgE in a dose-dependent manner with ID50 (the dose required for 50% inhibition of histamine release) of 2.2 x 10(-8) M. Histamine release stimulated with 12-0-tetradecanoyl-phorbol-13-acetate(TPA) was also suppressed by K-252a with maximal inhibition of 48.0 +/- 9.3% at 10(-7) M. In contrast, K-252a did not inhibit the release of histamine in response to FMLP and ionophore A23187. Another inhibitor of PKC, H-7, exhibited a dose-dependent inhibition of anti-IgE-induced histamine release with ID50 of 8.6 x 10(-4) M. H-8 and HA1004, which closely resemble H-7 in chemical structure but are less potent in inhibiting PKC, did not inhibit histamine release stimulated with anti-IgE, but rather enhanced the release at higher concentrations. These results strongly suggest that PKC activation plays a crucial role in the mediation of IgE-mediated histamine release from human basophils.
在本研究中，我们调查了钙和磷脂依赖性蛋白激酶（蛋白激酶C，PKC）在调节人嗜碱性粒细胞组胺释放中的作用。一种新型强效PKC抑制剂K-252a以剂量依赖性方式抑制抗IgE诱导的组胺释放，其半数抑制剂量（ID50，即抑制50%组胺释放所需的剂量）为2.2×10⁻⁸M。12-0-十四烷酰佛波醇-13-乙酸酯（TPA）刺激引起的组胺释放也被K-252a抑制，在10⁻⁷M时最大抑制率为48.0±9.3%。相比之下，K-252a不抑制对FMLP和离子载体A23187的组胺释放反应。另一种PKC抑制剂H-7对抗IgE诱导的组胺释放表现出剂量依赖性抑制，ID50为8.6×10⁻⁴M。化学结构与H-7相似但抑制PKC能力较弱的H-8和HA1004不抑制抗IgE刺激的组胺释放，反而在较高浓度下增强释放。这些结果强烈表明PKC激活在介导人嗜碱性粒细胞IgE介导的组胺释放中起关键作用。
