The role of tachykinin receptor antagonists in the prevention of bronchial hyperresponsiveness, airway inflammation and cough

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.

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