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Serotonin downregulates alveolar epithelial fluid transport via a direct inhibition of ENaC
Author(s) -
Goolaerts Arnaud,
Roux Jérémie,
Ganter Michael,
Shlyonsky Vadim,
Mies Frédérique,
Matthay Michael,
Sohraby Sarah,
Pittet JeanFrançois
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a553-d
Subject(s) - amiloride , serotonin , epithelial sodium channel , chemistry , a549 cell , receptor , medicine , pharmacology , endocrinology , biophysics , biology , cell , biochemistry , sodium , organic chemistry
Serotonin is released in the respiratory track under various physiological conditions such as hypoxia and epithelial stretch, and may participate to the inflammatory response associated with these pathological conditions. However, the effect of serotonin on alveolar epithelial fluid transport is unknown. In this study, we found serotonin causes a dose‐dependent decrease in the amiloride‐sensitive current across A549, rat ATII and human ATII cells with an IC50 of 1mM and kinetics suggesting a direct inhibition of ENaC. We established a dose‐response curve in A549 cells for amiloride in the presence of 2mM serotonin using whole cell patch‐clamp technique. The IC50 of amiloride under control conditions or under 2mM serotonin are comparable, indicating that serotonin does not compete with amiloride and interacts with another site of ENaC. Furthermore, pre‐treatment with Bapta‐AM and the non selective antagonist to the 5‐HT2 receptor that have been identified in both rat and human did not impair the effect of serotonin on Isc, indicating that this effect is not receptor‐mediated. Finally, our data show that alveolar instillation of serotonin causes a dose‐dependent decrease of the alveolar fluid transport in mice. All together our results indicate that serotonin is a potential endogenous inhibitor of the ENaCs in ATII cells by direct interaction with the channel.