Her E, Weissman B A, Zor U
Department of Hormone Research, The Weizmann Institute of Science, Rehovot, Israel.
Biochim Biophys Acta. 1990 Feb 19;1051(2):203-6. doi: 10.1016/0167-4889(90)90195-j.
Rat basophilic leukemia (RBL-2H3) cells serve as a model to examine the role of elevated internal Ca2+ concentration ([Ca2+]i), following antigen (DNP10BSA)-induced stimulation of leukotriene C4 (LTC4) formation. A novel action of hydrocortisone (HC), to reduce increased [Ca2+]i and consequently inhibit LTC4 formation is assessed. Half-maximal time for elevation of [Ca2+]i induced by antigen was less than 1 min, and maximal elevation of [Ca2+]i (3-fold increase) was reached within 2-3 min. This high [Ca2+]i level waned gradually by 27% during 20 min of incubation. For induction of LTC4 formation, however, there was a refractory period of about 2 min, and half-maximal elevation was at 11 min. Following pretreatment with HC, the antigen-stimulated increase in [Ca2+]i was stunted by 41% at 2-3 min and by 73% at 20 min. LTC4 formation was almost abolished. There was a lag period of at least 2 h to observe any inhibition in both parameters, and the maximal inhibition was about 4 h. Cycloheximide, and receptor antagonist to glucocorticosteroid (RU486) completely prevented the inhibitory effects of HC on elevated [Ca2+]i and LTC4 formation. Estradiol and aldosterone (each at 2.10(-6) M) were virtually inactive, while another glucocorticosteroid, dexamethasone (2.10(-7) M) markedly suppressed antigen induction in both parameters. It is proposed that the inhibitory effect of HC on the formation of LTC4 could be attributed mainly to its ability to reduce elevated [Ca2+]i.
大鼠嗜碱性白血病（RBL - 2H3）细胞可作为一个模型，用于研究在抗原（二硝基苯基化牛血清白蛋白，DNP10BSA）诱导下，细胞内钙离子浓度（[Ca2+]i）升高对白三烯C4（LTC4）生成的作用。本研究评估了氢化可的松（HC）的一种新作用，即降低升高的[Ca2+]i，从而抑制LTC4的生成。抗原诱导[Ca2+]i升高的半数最大时间不到1分钟，在2 - 3分钟内达到[Ca2+]i的最大升高（增加3倍）。在孵育20分钟期间，这种高[Ca2+]i水平逐渐下降了27%。然而，对于LTC4的生成诱导，存在约2分钟的不应期，半数最大升高出现在11分钟。用HC预处理后，在2 - 3分钟时，抗原刺激引起的[Ca2+]i升高受到41%的抑制，在20分钟时受到73%的抑制。LTC4的生成几乎被完全抑制。在观察到对这两个参数的任何抑制作用之前，至少有2小时的延迟期，最大抑制作用约为4小时。环己酰亚胺（一种糖皮质激素受体拮抗剂，RU486）完全阻止了HC对升高的[Ca2+]i和LTC4生成的抑制作用。雌二醇和醛固酮（均为2×10^(-6) M）几乎没有活性，而另一种糖皮质激素地塞米松（2×10^(-7) M）则显著抑制了这两个参数的抗原诱导。研究表明，HC对LTC4生成的抑制作用可能主要归因于其降低升高的[Ca2+]i的能力。
