Bile acids differentially regulate longitudinal smooth muscle contractility in everted mouse ileum

Area of Science:

• Gastroenterology
• Pharmacology
• Physiology

Background:

• Bile acids influence gastrointestinal (GI) motility through incompletely understood mechanisms.
• Traditional tissue bath assays may not fully reflect in vivo conditions for studying bile acid effects on gut motility.
• Direct mucosal application might be crucial for observing certain bile acid-induced contractile responses.

Purpose of the Study:

• To assess the feasibility of quantifying longitudinal smooth muscle contractile responses to bile acids in intact, everted mouse ileum segments.
• To investigate the specific effects of various bile acids on intestinal contractility.
• To identify the receptors and signaling pathways involved in bile acid-mediated GI motility.

Main Methods:

• Isolation and gentle eversion of intact mouse ileum segments.
• Mounting everted ileum in tissue baths for isometric force transduction.
• Dose-dependent administration of individual bile acids and receptor agonists to quantify contractile responses.

Main Results:

• Ursodeoxycholic acid significantly increased contractile responses in a dose-dependent manner.
• Deoxycholic acid exhibited biphasic effects, stimulating contractility at low doses and inhibiting at high doses.
• Chenodeoxycholic acid, glycocholic acid, and lithocholic acid did not affect contractility.
• The prokinetic effects of ursodeoxycholic acid were mimicked by TGR5 and muscarinic acetylcholine receptor agonists.
• Agonists for nuclear receptors (FXR, GR, PXR, VDR) and EGFR did not alter contractile patterns.

Conclusions:

• Gentle eversion of intact mouse ileum is a viable method for studying bile acid-induced smooth muscle contractility.
• Ursodeoxycholic acid and low-dose deoxycholic acid possess prokinetic effects on GI motility.
• TGR5 and muscarinic acetylcholine receptors mediate the prokinetic actions of specific bile acids.