Interplay between mast cells, enterochromaffin cells and afferent nerves innervating the gastrointestinal tract and influence of ageing

This thesis addressed the sensory functions of the gastrointestinal (GI) tract with an emphasis on the interaction between afferents nerves and other cell types such as enterochromaffin (EC) cells and mast cells, and also investigated the influence of ageing on these interactions.

Studies on mice focused on TRPA1, a central molecule in nociception and inflammation. TRPA1 signaling induced by allyl isothiocyanate (AITC) comprised direct activation of TRPA1 on extrinsic afferents, indirect activation of 5-HT3 receptors on extrinsic afferents following 5-HT release form EC cells and indirect signals evoked by contractions. TRPA1 signaling was attenuated with advanced age. This could be attributed to reduced primary afferent innervation and decreased gene expression of 5-HT3 in the gut wall.

Sensory functions of human GI tract were investigated morphologically and functionally. Some changes were identified in aged human bowel, including increased EC cells, mast cells, decreased sensory innervation and enhanced mast cell-afferent associations. Afferent activities were recorded from isolated human bowel using a novel in vitro model, allowing direct characterization of the mechanical and chemical sensitivities of human gastrointestinal afferents.