Journal: Translational Pediatrics
Article Title: Chenodeoxycholic acid activates the TGR5/TRPA1-5-HT pathway to regulate intestinal motility in breastfed infants and mouse models
doi: 10.21037/tp-2025-100
Figure Lengend Snippet: Impact of serotonin pathway inhibition on CDCA-induced changes in intestinal motility as described in . After CDCA treatment (20 mg/kg via enema for 7 days), mice received inhibitors targeting different components of the serotonin signaling pathway. (A) Representative images of GI transit distance after carmine red gavage (30 min) in mice treated with: Control (PBS), CDCA only, Alosetron (5-HT3R antagonist, 1 mg/kg, blocking serotonin receptor signaling), GR113808 (5-HT4R antagonist, 1 mg/kg, blocking a different serotonin receptor subtype), or LX1606 (Tph1 inhibitor, 200 mg/kg, blocking serotonin synthesis). The red arrow as in . (D) Similar transit images for mice treated with Control, CDCA only, SBI-115 (TGR5 antagonist, 15 mg/kg, blocking the bile acid receptor upstream of serotonin signaling), or HC-030031 (TRPA1 inhibitor, 150 mg/kg, blocking another upstream component in the signaling pathway). The red arrow as in . (B,E) Representative images of fecal appearance from corresponding treatment groups. (C,F) Quantitative measurements of fecal water content, GI transit time, colonic transit distance (60 min post-carmine), and ELISA results for 5-HT and cAMP levels in colon tissue for all treatment groups. The experimental design systematically targets different points in the TGR5/TRPA1-5-HT signaling axis as detailed in the Methods section (2.8 and 2.9). Data were presented as mean ± SD. *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001. n=5/group. 5-HT, 5-hydroxytryptamine (serotonin); 5-HT3R, 5-HT receptor 3; 5-HT4R, 5-HT receptor 4; cAMP, cyclic adenosine monophosphate; CDCA, chenodeoxycholic acid; ELISA, enzyme-linked immunosorbent assay; GI, gastrointestinal; PBS, phosphate-buffered saline; SD, standard deviation; Tph1, tryptophan hydroxylase 1; TRPA1, transient receptor potential A1.
Article Snippet: LX1606 (T171759, Aladdin; listed in ) was used as a Tph1 inhibitor , while alosetron (A125218, Aladdin; listed in ) and GR113808 (HY-103152, Mce; listed in ) served as 5-HT3R and 5-HT4R antagonists, respectively ( , ).
Techniques: Inhibition, Control, Blocking Assay, Enzyme-linked Immunosorbent Assay, Saline, Standard Deviation
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