Several recent observations suggest that
tachykinins, such as
substance P and
neurokinin A, might be involved in the pathogenesis of bronchopulmonary alterations. Progress in investigations on the physiological and pathological roles of
tachykinins has been greatly facilitated by the availability of a number of highly selective nonpeptide antagonists for
tachykinin neurokinin 1, 2 and 3 (NK1, NK2 and NK3) receptors. The use of selective
tachykinin NK2 receptor antagonists suggests that
tachykinin NK2 receptor stimulation plays an important role in the development of
airway hyperresponsiveness in the guinea-pig. Others studies have also indicated that
tachykinin NK1-receptors are involved in immediate or delayed
neurogenic inflammation including microvascular leakage and the subsequent increase in
plasma protein extravasation. A role for the sensory
neuropeptide system has also been proposed in
cough, as shown by the observation that the
antitussive effect of
tachykinin NK2 receptor antagonists has clearly been demonstrated in several experimental conditions, but the effect of
tachykinin NK1 receptor antagonists is still debated. Taken together, the results obtained with the various selective receptor antagonists provide pharmacological evidence that
tachykinins play a role in delayed bronchopulmonary alterations and suggest that
tachykinin receptor antagonists may be useful for investigating mechanisms and possibly reducing airway functional alterations in asthmatic patients.