Peripheral tachykinin receptors as targets for new drugs

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 neu rons from which are released by stimuli having both pathological and physio logical relevance. The most studied effects produced by tachykinins in thes e systems are smooth muscle contraction, plasma protein extravasation, mucu s secretion and recruitment/activation of immune cells. The use of tachykin in receptor-selective antagonists and knockout animals has enabled to ident ify the involvement of tachykinin NK1, NTK2 and NK3 receptors as mediators of peripheral effects of tachykinins in different systems /species. The bul k of data obtained in experimental animal models suggests that tachykinins could contribute to the genesis of symptoms accompanying various human dise ases including asthma/bronchial hyperreactivity, cystitis of various aetiol ogy, inflammatory bowel diseases and irritable bowel syndrome. Tachykinin r eceptor antagonists are expected to afford therapeutically relevant effects . (C) 2001 Elsevier Science B.V. All rights reserved.