Role of tachykinins in bronchial hyper-responsiveness.
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.
Reynolds
P N
PN
Department of Thoracic Medicine Lung Research Laboratory, Hanson Centre for Cancer Research, Royal Adelaide Hospital, Australia.
Holmes
M D
MD
Scicchitano
R
R
D000402:Airway Obstruction; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects / Q000294:innervation; D016535:Bronchial Hyperreactivity / Q000378:metabolism / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D015320:Tachykinins / Q000378:metabolism / Q000502:physiology*
D018039:Receptors, Tachykinin; D015320:Tachykinins; D013373:Substance P; D002211:Capsaicin