Morita Y, Siraganian R P
J Immunol. 1981 Oct;127(4):1339-44.
This study evaluated the effect of inhibitors of transmethylation on histamine release from rat mast cells and rat basophilic leukemia cells. IgE-mediated histamine release from rat basophilic leukemia cells (RBL-2H3 cells) was inhibited by 3-deazaadenosine (DZA) in the presence of L-homocysteine thiolactone (Hcy) or the combination of adenosine, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), and Hcy in a dose-dependent fashion. There were no significant changes in the cellular cAMP levels by these inhibitors. Histamine release induced by anti-IgE or dextran from normal rat mast cells was also blocked by DZA plus Hcy in a dose-dependent manner. DZA at 10(-3) M in the presence of 10(-4) M Hcy or the combination of 10(-3) M adenosine, 10(-4) M EHNA, and 10(-3) M Hcy inhibited lipid (perhaps phospholipid) methylation into RBL-2H3 cells without affecting choline incorporation. In the presence of 10(-3) M DZA plus 10(-4) M Hcy there was a 170-fold increase in [35S]AdoHcy with the concomitant appearance of 3-deaza-AdoHcy when the cells were incubated with [35S]methionine, thus indicating that these drugs inhibited methylation reaction(s) through the intracellular accumulation of AdoHcy and 3-deaza-AdoHcy. In contrast, histamine release from rat mast cells induced by the calcium ionophore A23187, compound 48/80, polymyxin B, or ATP was not inhibited by these compounds. These results suggest that IgE- or dextran-mediated histamine release involves methylation reactions(s), whereas the other secretagogues bypass this early step.
本研究评估了转甲基化抑制剂对大鼠肥大细胞和大鼠嗜碱性白血病细胞组胺释放的影响。在L-高半胱氨酸硫内酯（Hcy）存在的情况下，3-脱氮腺苷（DZA）或腺苷、赤藓红-9-(2-羟基-3-壬基)腺嘌呤（EHNA）与Hcy的组合，以剂量依赖的方式抑制了大鼠嗜碱性白血病细胞（RBL-2H3细胞）中IgE介导的组胺释放。这些抑制剂对细胞内cAMP水平无显著影响。DZA加Hcy也以剂量依赖的方式阻断了抗IgE或右旋糖酐诱导的正常大鼠肥大细胞组胺释放。在10(-4)M Hcy存在下的10(-3)M DZA或10(-3)M腺苷、10(-4)M EHNA和10(-3)M Hcy的组合，抑制了RBL-2H3细胞中的脂质（可能是磷脂）甲基化，而不影响胆碱掺入。当细胞与[35S]甲硫氨酸一起孵育时，在10(-3)M DZA加10(-4)M Hcy存在的情况下，[35S]腺苷高半胱氨酸（AdoHcy）增加了170倍，同时出现了3-脱氮-AdoHcy，这表明这些药物通过AdoHcy和3-脱氮-AdoHcy的细胞内积累抑制了甲基化反应。相反，钙离子载体A23187、化合物48/80、多粘菌素B或ATP诱导的大鼠肥大细胞组胺释放不受这些化合物的抑制。这些结果表明，IgE或右旋糖酐介导的组胺释放涉及甲基化反应，而其他促分泌剂绕过了这一早期步骤。
