1. Sensory afferent fibres mediate important protective reflexes in the lung. Small, unmyelinated C-fibre nerves have both sensory afferent and effector functions. C-fibres contain a number of
neuropeptides, including the
tachykinins, which have pro-inflammatory effects in the airways. Following stimulation with
capsaicin and other stimuli,
neuropeptides are released from the nerve endings, either directly or by axonal reflexes. 2. Important
tachykinin effects include smooth muscle contraction, vasodilatation and oedema, mucus secretion and inflammatory cell activation. There are also trophic effects, including proliferation of fibroblasts, smooth muscle and epithelial cells. 3.
Tachykinins mediate their effects by binding to G-proteinlinked receptors. Receptor-specific agonists and antagonists are available, which have helped clarify the effects of
tachykinins. These agents may have therapeutic potential. 4.
Tachykinins are degraded by the
enzyme neutral endo-
peptidase. 5. Studies in humans in vivo show an increase in airways resistance following challenge with
tachykinins. There is some evidence for an increase in
tachykinins and their receptors in airway
inflammation, but this has not been found in all studies. A reduction in
neutral endopeptidase has been seen in some animal models of airway
inflammation, but this has not been shown in human disease. 6. Trials of
tachykinin receptor antagonists in human
asthma have begun, but it is too early to say what their therapeutic impact will be.