Figure 3. Neuro-humoral signalling of BAs and TGR5 in the gastrointestinal wall.

(1) In the small intestine, luminal BAs can activate TGR5 on L cells to induce secretion of the hormone GLP-1. (2) In the colon, luminal BAs can activate TGR5 on EC cells to stimulate secretion of 5–HT, which activates 5–HT₄ receptors on intrinsic primary afferent neurons, which release CGRP, a mediator of the ascending and descending components of the peristaltic reflex. Absorbed BAs may directly activate TGR5 on enteric neurons to induce release of CGRP. (3) TGR5 is expressed by gastric myocytes, where activation by absorbed BAs can inhibit contractility. (4) Absorbed BAs may activate TGR5 on colonocytes to inhibit chloride secretion. (5) Absorbed BAs activate TGR5 on colonic macrophages to suppress secretion of tumour necrosis factor α and dampen inflammation. (6) By analogy to the skin, absorbed BAs may activate TGR5 on primary sensory neurons that transmit irritant signals to the spinal cord.