Lubiprostone activates CFTR, but not ClC-2, via the prostaglandin receptor (EP4)

Yohei Norimatsu, Aurelia R. Moran, Kelvin D. MacDonald

    Research output: Contribution to journalArticlepeer-review

    32 Scopus citations


    The goal of this study was to determine the mechanism of lubiprostone activation of epithelial chloride transport. Lubiprostone is a bicyclic fatty acid approved for the treatment of constipation [1]. There is uncertainty, however, as to how lubiprostone increases epithelial chloride transport. Direct stimulation of ClC-2 and CFTR chloride channels as well as stimulation of these channels via the EP4 receptor has been described [2-5]. To better define this mechanism, two-electrode voltage clamp was used to assay Xenopus oocytes expressing ClC-2, with or without co-expression of the EP4 receptor or β adrenergic receptor (βAR), for changes in conductance elicited by lubiprostone. Oocytes co-expressing CFTR and either βAR or the EP4 receptor were also studied. In oocytes co-expressing ClC-2 and βAR conductance was stimulated by hyperpolarization and acidic pH (pH=6), but there was no response to the β adrenergic agonist, isoproterenol. Oocytes expressing ClC-2 only or co-expressing ClC-2 and EP4 did not respond to the presence of 0.1, 1, or 10μM lubiprostone in the superperfusate. Oocytes co-expressing CFTR and βAR did not respond to hyperpolarization, acidic pH, or 1μM lubiprostone. However, conductance was elevated by isoproterenol and inhibited by CFTRinh172. Co-expression of CFTR and EP4 resulted in lubiprostone-stimulated conductance, which was also sensitive to CFTRinh172. The EC50 for lubiprostone mediated CFTR activation was ∼10nM. These results demonstrate no direct action of lubiprostone on either ClC-2 or CFTR channels expressed in oocytes. However, the results confirm that CFTR can be activated by lubiprostone via the EP4 receptor in oocytes.

    Original languageEnglish (US)
    Pages (from-to)374-379
    Number of pages6
    JournalBiochemical and Biophysical Research Communications
    Issue number3
    StatePublished - Sep 28 2012


    • CFTR
    • Chloride channel
    • ClC-2
    • Lubiprostone
    • Prostaglandin

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Molecular Biology
    • Cell Biology


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