Pharmacologic characterization of a novel histamine receptor on human eosinophils.
Pharmacologic characterization of a novel histamine receptor on human eosinophils.
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DOI：
10.1164/ajrccm.149.6.8004306
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发表时间：
1994-06
影响因子：
24.7
通讯作者：
Donald G. Raible;Terrence Lenahan;Yelena Fayvilevich;Robert Kosinski;Edward S. Schulman
中科院分区：
文献类型：
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作者：
Donald G. Raible;Terrence Lenahan;Yelena Fayvilevich;Robert Kosinski;Edward S. Schulman
越来越多的人认识到，肺肥大细胞介质不仅产生急性哮喘症状，而且还导致额外的促炎细胞（如嗜酸性粒细胞）的募集和激活。组胺是肥大细胞的主要介质之一，已知对嗜酸性粒细胞功能有许多影响。组胺的这些作用是由嗜酸性粒细胞表面的不同受体介导的，其中只有一些已被表征。先前的研究表明嗜酸性粒细胞具有非h1，非h2组胺受体，介导组胺的趋化作用。我们之前观察到，组胺诱导的人嗜酸性粒细胞胞质钙的增加不能被经典的H1或H2拮抗剂阻断，但可以被H3拮抗剂硫哌丁胺抑制。本研究的目的是进一步表征这种钙联组胺受体的药理学特性。使用富拉-2负载嗜酸性粒细胞测量细胞质钙的浓度，我们检查了额外的组胺受体拮抗剂和激动剂的作用。我们发现H3拮抗剂硫哌丁胺、丙咪胺和布里马胺的pKb（分别为8.1、7.6和7.2）与中枢神经系统中H3受体的pKb相似，这表明嗜酸性粒细胞组胺受体与H3受体相似。然而，当测试已知的H3激动剂（[R]- α -甲基组胺，N α -甲基组胺）的活性时，这些化合物的效力远低于组胺本身的效力，这表明H3受体与这种嗜酸性组胺受体之间存在显着差异。（摘要删节250字）
There is increased recognition that lung mast cell mediators not only produce the symptoms of acute asthma, but also result in the recruitment and activation of additional proinflammatory cells, such as eosinophils. Histamine, one of the major mast cell mediators, is known to have numerous effects on eosinophil function. These effects of histamine are mediated by distinct receptors on the surface of eosinophils, only some of which have been characterized. Prior studies have suggested that eosinophils have non-H1, non-H2 histamine receptors which mediate the chemotactic effects of histamine. We observed previously that the histamine-induced increase in cytosolic calcium in human eosinophils could not be blocked by classic H1 or H2 antagonists, but could be inhibited by the H3 antagonist thioperamide. The purpose of this study was to further characterize the pharmacologic properties of this calcium-linked histamine receptor. Using Fura-2 loaded eosinophils to measure the concentration of cytosolic calcium, we examined the effect of additional histamine receptor antagonists and agonists. We found that the pKb for the H3 antagonists thioperamide, impromidine, and burimamide (8.1, 7.6, and 7.2, respectively), were similar to those reported for H3 receptors in the central nervous system, suggesting that the eosinophil histamine receptor was similar to H3 receptors. However, when the known H3 agonists were tested for activity ([R]-alpha-methylhistamine, N alpha-methylhistamine), the potencies of these compounds were much less than the potency of histamine itself, indicating a significant difference between H3 receptors and this eosinophil histamine receptor.(ABSTRACT TRUNCATED AT 250 WORDS)