Tachykinins: role in human gastrointestinal tract physiology and pathology

Tachykinins (TKs) and their receptors (NK1, NK2 and NK3), which are diffusely expressed in the human gastrointestinal tract, represent an endogenous modulator system regulating enteric secretomotor functions, inflammatory and immune responses, and visceral hypersensitivity, mainly during pathological gut diseases. Pathophysiological implications of TKs in the digestive tract include changes in TK innervation, in the expression of TKs and TK receptors, which result in inflammation- and immune-induced disturbances of gut functions, such as dysmotility (diarrhoea/constipation), secretory diarrhoea and visceral hyperalgesia. Increasing evidence correlates all these TKergic system abnormalities with gastrointestinal diseases of different etiology (i.e. inflammatory bowel diseases, irritable bowel syndrome). Accordingly, TK receptors have been identified as novel targets for the development of new therapeutic agents for clinical use. Available preclinical findings have shown that TK antagonists could counteract the most significant symptoms characterizing these gut diseases.