THE ROLE OF TACHYKININ RECEPTOR ANTAGONISTS IN THE PREVENTION OF BRONCHIAL HYPERRESPONSIVENESS, AIRWAY INFLAMMATION AND COUGH

Several recent observations suggest that tachykinins, such as substanc e P and neurokinin A, might be involved in the pathogenesis of broncho pulmonary 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 antagonis ts 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 de velopment of airway hyperresponsiveness in the guinea-pig, Others stud ies have also indicated that tachykinin NK1-receptors are involved in immediate or delayed neurogenic inflammation including microvascular l eakage and the subsequent increase in plasma protein extravasation, A role for the sensory neuropeptide system has also been proposed in cou gh, as shown by the observation that the antitussive effect of tachyki nin NK2 receptor antagonists has clearly been demonstrated in several experimental conditions, but the effect of tachykinin NK1 receptor ant agonists is still debated, Taken together, the results obtained with t he various selective receptor antagonists provide pharmacological evid ence that tachykinins play a role in delayed bronchopulmonary alterati ons and suggest that tachykinin receptor antagonists may be useful for investigating mechanisms and possibly reducing airway functional alte rations in asthmatic patients.