Figure 2.

The FXR in regulation of bile acid (BA)-induced colonic fluid secretion. Increased colonic delivery of dihydroxy BAs, such as DCA and CDCA, increases epithelial levels of the intracellular second messengers, Ca²⁺ and adenosine 3′,5′-cyclic monophosphate (cAMP), either by direct (solid black lines) or indirect actions, involving the enteric nervous system (ENS) and the mucosal immune system (MIS) (dashed black lines). These second messengers interact with specific transport proteins to promote transepithelial Cl^- secretion, thereby creating an osmotic driving force for fluid secretion, ultimately leading to the onset of diarrhea. Treatment with FXR agonists (blue lines) dampens epithelial fluid secretion by down-regulating the activity and expression of basolateral Na⁺/K⁺ adenosine triphosphatase (ATPase) pumps and apical cystic fibrosis transmembrane conductance regulator (CFTR) channels, key transport proteins of the Cl^- secretory pathway.