ROLE OF TACHYKININS IN BRONCHIAL HYPERRESPONSIVENESS

1. Sensory afferent fibres mediate important protective reflexes in th e lung. Small, unmyelinated C-fibre nerves have both sensory afferent and effector functions. C-fibres contain a number of neuropeptides, in cluding the tachykinins, which have proinflammatory effects in the air ways. Following stimulation with capsaicin and other stimuli, neuropep tides are released from the nerve endings, either directly or by axona l reflexes. 2. Important tachykinin effects include smooth muscle cont raction, vasodilatation and oedema, mucus secretion and inflammatory c ell activation. There are also trophic effects, including proliferatio n of fibroblasts, smooth muscle and epithelial cells. 3. Tachykinins m ediate their effects by binding to G-protein-linked receptors. Recepto r-specific agonists and antagonists are available, which have helped c larify the effects of tachykinins. These agents may have therapeutic p otential. 4. Tachykinins are degraded by the enzyme neutral endopeptid ase. 5. Studies in humans in vivo show an increase in airways resistan ce following challenge with tachykinins. There is some evidence for an increase in tachykinins and their receptors in airway inflammation, b ut this has not been found in all studies. A reduction in neutral endo peptidase has been seen in some animal models of airway inflammation, but this has not been shown in human disease.6. Trials of tachykinin r eceptor antagonists in human asthma have begun, but it is too early to say what their therapeutic impact will be.