TACHYKININ RECEPTORS AND NON-CHOLINERGIC BRONCHOCONSTRICTION IN THE ANAESTHETIZED GUINEA-PIG

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Abstract
1. Bronchoconstriction can be evoked by electrical stimulation of the vagus nerves in the presence of atropine. We have used novel, highly selective tachykinin receptor antagonists, together with a procedure for on-line, breath-by-breath analysis of total lung resistance (R(L), subtractor method) and dynamic lung compliance (C(dyn)), to investigate the role of tachykinins in this response in anaesthetized, paralysed guinea-pigs. 2. In the presence of 1 mg/kg phosphoramidon (a neutral endopeptidase inhibitor), CP 96345 (the non-peptide NK1 selective antagonist) at 200 nmol/kg had no effect on the increase in R(L) caused by vagal stimulation, but significantly inhibited the associated decrease in C(dyn). 3. The NK2 selective antagonist, MDL 29913 (1 mu mol/kg), significantly antagonized the changes in both R(L) and C(dyn). In the absence of phosphoramidon, MDL 29913 again significantly inhibited the changes in R(L) and C(dyn) although CP 96345 no longer had any effect. 4. The non-peptide NK2 selective antagonist, SR 48968 (100 nmol/kg), also effectively inhibited the responses to vagal stimulation and was more potent than MDL 29913. 5. These results emphasize the importance of the NK2 receptor system in mediating non-cholinergic bronchoconstriction evoked by vagal stimulation in the guinea-pig.