Lubiprostone (RU-0211), an activator of ClC-2 chloride channels, is used in the therapy of idiopathic chronic constipation.

Lubiprostone在T84单层细胞中引起强烈的分泌反应，并且通过cAMP水平的提升表现出其对EP(4)受体阻断的敏感性。[1] 在大鼠和人类的胃纵向肌肉中，Lubiprostone可引起收缩，这种收缩被EP(1)受体拮抗剂预处理所抑制，但不受EP(3)或EP(4)受体拮抗剂的影响。Lubiprostone还能减少大鼠和人类结肠环形肌电刺激引起的神经收缩。[2] Lubiprostone (1 mM)在较低的I(sc)反应下，仍然能刺激TER的较高上升，与非选择性分泌激动剂PGE(2) (1 mM)相比。Lubiprostone显著降低了(3)H标记的甘露醇从粘膜到浆液的通量，恢复了正常组织水平，并将occludin的定位恢复到紧密连接。[3] Lubiprostone在T84细胞中引起的I(sc)增加与最大值相当。Lubiprostone诱导的碘离子外流约为用forskolin获得的80%。Lubiprostone通过cAMP、蛋白激酶A和增加顶膜CFTR蛋白的方式，激活T84细胞中Cl(-)的分泌。[4] Lubiprostone在1-3000 nM的八个浓度级别上施加到小肠黏膜，以浓度依赖的方式引起Isc的增加，EC50为42.5 nM。在1-3000 nM的八个浓度范围内，施加到结肠黏膜的Lubiprostone也以浓度依赖的方式引起Isc的增加，EC50为31.7 nM。[5]

Lubiprostone 在小鼠肠道引发CdCl(2)-不敏感的分泌反应，但在Cftr-null小鼠中未能引起肠道Cl(-)分泌。[1]

Fluorescence polarization-based competition assay: Inhibition constants ( Ki ) for the antagonists are determined by addition of the IAP protein constructs to wells containing serial dilutions of the antagonists or the peptide AVPW, and the Hid-FAM probe or AVP-diPhe-FAM probe, as appropriate, in the polarization buffer. Samples are read after a 30-minute incubation. Fluorescence polarization values are plotted as a function of the antagonist concentration, and the IC50 values are obtained by fitting the data to a 4-parameter equation using software. Ki values for the antagonists are determined from the IC50 valued.