The gastrointestinal endothelin system: receptors, cellular actions, and involvement in gastrointestinal disorders

The gastrointestinal endothelin system regulates vital processes including motility, secretion, sensation, and inflammation. Endothelin-1 acts via endothelin A and B receptors expressed on diverse intestinal cells. Dysregulation of endothelin signaling underlies common gastrointestinal disorders such as inflammatory bowel disease and irritable bowel syndrome. Aberrant endothelin-1 production and endothelin A receptor activation contribute to the inflammation, pain hypersensitivity, impaired epithelial function, and smooth muscle hypercontractility characteristic of these diseases. Endothelin receptor antagonists may provide therapies for managing related symptoms. However, knowledge gaps exist regarding cell-specific signaling pathways, regulatory factors, and precise roles in intestinal pathologies. Elucidating these details and translating insights into improved endothelin-targeted treatments could enable novel strategies for restoring homeostasis and improving patient outcomes. Advancing understanding of tissue-specific endothelin system functions represents a promising research avenue for unraveling disease mechanisms and developing new therapies for gastrointestinal disorders involving dysfunction of this regulatory axis.