Estradiol augments while tamoxifen inhibits rat mast cell secretion.
Estradiol augments while tamoxifen inhibits rat mast cell secretion.
复制标题
雌二醇增强而他莫昔芬抑制大鼠肥大细胞分泌。
DOI：
10.1159/000236217
复制
发表时间：
1992
影响因子：
2.8
通讯作者：
Theoharides,TC
中科院分区：
文献类型：
--
作者：
Vliagoftis,H;Dimitriadou,V;Boucher,W;Rozniecki,JJ;Correia,I;Raam,S;Theoharides,TC
肥大细胞因参与过敏反应而被广泛研究，在过敏反应中，肥大细胞分泌许多强大的介质来响应免疫球蛋白E和特定的抗原。然而，它们也是由神经肽触发的，它们被发现与神经元密切接触，在血管水肿、间质性膀胱炎和肠易激疾病等疾病中被激活，这些疾病在女性中的患病率要高得多。在纯化的大鼠腹膜肥大细胞上实验，17β-雌二醇促进组胺和5-羟色胺的分泌，从1μM开始，并呈剂量依赖关系，无论是肥大细胞促分泌剂化合物48/80还是神经肽P物质。但17β-雌二醇不能增加免疫球蛋白E和特异性抗血清刺激的肥大细胞的分泌，表明免疫刺激受到不同的调节。睾酮抑制化合物48/80诱导的分泌。他莫昔芬是一种用于治疗乳腺癌的雌激素受体拮抗剂，它可以抑制化合物48/80或P物质引发的纯化的大鼠腹膜肥大细胞的5-羟色胺和组胺释放。他莫昔芬还抑制因化合物48/80引起的细胞外钙离子内流而产生的细胞内游离钙离子的增加。此外，他莫昔芬拮抗佛波酯和阳离子载体A23187对肥大细胞分泌的协同作用，提示他莫昔芬的抑制作用可能是通过调节蛋白激酶C的活性而实现的。因此，他莫昔芬可能通过阻断雌激素受体和抑制肥大细胞的分泌，对其他神经免疫内分泌疾病起到有益的作用。
Mast cells have been studied extensively for their involvement in allergic reactions, where they secrete numerous powerful mediators in response to immunoglobulin E and specific antigens. However, they are also triggered by neuropeptides, they have been found in close contact with neurons, and they are activated in diseases such as angioedema, interstitial cystitis and irritable bowel disease, the prevalence of which is much higher in women. When tested on purified rat peritoneal mast cells, 17β-estradiol augmented secretion of histamine and serotonin, starting at 1 μMand in a dose-dependent manner, whether stimulated by the mast cell secretagogue compound 48/80 or the neuropeptide substance P. However, 17β-estradiol did not augment mast cell secretion stimulated by immunoglobulin E and specific antiserum indicating that immunologic stimulation is under different regulation. Testosterone inhibited secretion induced by compound 48/80. Tamoxifen, an estrogen receptor antagonist used in the treatment of breast cancer, inhibited serotonin and histamine release from purified rat peritoneal mast cells triggered by compound 48/80 or substance P. Tamoxifen also inhibited the increase in intracellular free Ca2+originating from an influx of extracellular Ca2+in response to compound 48/80. Moreover, tamoxifen antagonized the synergistic effect of phorbol myristate and the cation ionophore A23187 on mast cell secretion, suggesting that tamoxifen’s inhibition may be due to regulation of protein kinase C activity. Tamoxifen may, therefore, have a beneficial effect in other neuroimmunoendocrine disorders both through estrogen receptor blockade and inhibition of mast cell secretion.