Affiliation: Department of Pharmacology, National University of Singapore, Faculty of Medicine, Bldg. MD2, 18Medical Drive, Singapore 117597
Tachykinins constitute a family of neuropeptides which share the common C-terminal sequence Phe-Xaa-Gly- Leu-Met-NH2. This sequence is critical for their interaction with specific receptors and for producing most of their biological effects. Tachykinins are widely distributed in the peripheral nervous system of the respiratory, urinary and gastrointestinal tract, stored in enteric neurons and in peripheral nerve endings of capsaicin sensitive primary afferent neurons from which they are released by stimuli having physiological as well as pathological relevance. The most studied effects produced by tachykinins in these systems are smooth muscle contraction, plasma protein extravasation, mucus secretion, and recruitment and activation of immune and inflammatory cells. In recent studies using experimental animal models, tachykinins have been shown to play an important role in several inflammatory conditions, such as airway inflammation and asthma, allergic contact dermatitis, arthritis, cystitis, inflammatory bowel disease, trinitrobenzenesulfonic acid -induced colitis, Clostridium difficile toxin A-induced-enteritis, and acute pancreatitis. The use of tachykinin receptor antagonists and gene-knockout animals has enabled identification of the role of tachykinins and their receptors in different disease conditions. The evidence obtained using animal models suggests that tachykinins could contribute to inflammation in various human diseases and points to the potential usefulness of tachykinin receptor antagonists as therapeutic targets.