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 neurons from which are released by stimuli having both pathological and physiological relevance. The most studied effects produced by tachykinins in these systems are smooth muscle contraction, plasma protein extravasation, mucus secretion and recruitment/activation of immune cells. The use of tachykinin receptor-selective antagonists and knockout animals has enabled to identify the involvement of tachykinin NK(1), NK(2) and NK(3) receptors as mediators of peripheral effects of tachykinins in different systems/species. The bulk of data obtained in experimental animal models suggests that tachykinins could contribute to the genesis of symptoms accompanying various human diseases including asthma/bronchial hyperreactivity, cystitis of various aetiology, inflammatory bowel diseases and irritable bowel syndrome. Tachykinin receptor antagonists are expected to afford therapeutically relevant effects.