Saeki T, Ohwaki K, Naya A, Kobayashi K, Ishikawa M, Ohtake N, Noguchi K
Tsukuba Research Institute, BANYU Pharmaceutical Co., Ltd., Okubo 3, Tsukuba, Ibaraki, 300-2611, Japan.
Biochem Biophys Res Commun. 2001 Mar 2;281(3):779-82. doi: 10.1006/bbrc.2001.4372.
CCR3 is expressed in a variety of leukocyte subsets, especially eosinophils, and may be involved in allergic disorders such as atopic asthma. To clarify the pathophysiological roles of CCR3 in allergic disorders, we developed a nonpeptidyl CCR3 antagonist. This antagonist, which is referred to as "Compound X," that inhibited the binding of [(125)I]Eotaxin to CHO cells transfected with human CCR3 with an IC(50) value of 2.3 nM. In human eosinophils, Compound X also inhibited Eotaxin-induced increases in intracellular Ca(2+) concentrations and chemotaxis. Thus, Compound X appears to be a highly potent CCR3 antagonist. These findings suggest that Compound X may be a useful tool for elucidating the pathophysiological roles of CCR3 in a variety of allergic disorders.
CCR3在多种白细胞亚群中表达，尤其是嗜酸性粒细胞，并且可能参与诸如特应性哮喘等过敏性疾病。为了阐明CCR3在过敏性疾病中的病理生理作用，我们开发了一种非肽类CCR3拮抗剂。这种拮抗剂，即“化合物X”，抑制[(125)I]嗜酸性粒细胞趋化因子与转染了人CCR3的CHO细胞的结合，IC(50)值为2.3 nM。在人嗜酸性粒细胞中，化合物X还抑制嗜酸性粒细胞趋化因子诱导的细胞内Ca(2+)浓度升高和趋化作用。因此，化合物X似乎是一种高效的CCR3拮抗剂。这些发现表明，化合物X可能是阐明CCR3在多种过敏性疾病中的病理生理作用的有用工具。
