sb9b00310_si_001.pdf (1.21 MB)
Identification of Three Antimicrobials Activating Serotonin Receptor 4 in Colon Cells
journal contribution
posted on 2019-11-12, 20:44 authored by Emily
A. Yasi, Aurelia A. Allen, Widianti Sugianto, Pamela Peralta-YahyaThe
serotonin receptor 4b (5-HTR4b) is expressed throughout
the gastrointestinal tract, and its agonists are used in the treatment
of irritable bowel syndrome with constipation (IBS-C). Today, there
are no rapid assays for the identification of 5-HTR4b agonists.
Here, we developed a luciferase-based 5-HTR4b assay capable
of assessing one compound per second with a 38-fold dynamic range
and nM limit of detection for serotonin. We used the assay to screen
more than 1000 natural products and anti-infection agents and identified
five new 5-HTR4b ligands: hordenine, halofuginone, proflavine,
ethacridine, and revaprazan. We demonstrate that hordenine (antibiofilm),
halofuginone (antiparasitic), and revaprazan (gastric acid reducer)
activate 5-HTR4b in human colon epithelial cells, leading
to increased cell motility or wound healing. The 5-HTR4b assay can be used to screen larger pharmaceutical libraries to identify
novel treatments for IBS-C. This work shows that antimicrobials interact
not only with the gut microbiota, but also with the human host.