TACHYKININ RECEPTORS AND NONCHOLINERGIC BRONCHOCONSTRICTION IN THE ANESTHETIZED GUINEA-PIG

1. Bronchoconstriction can be evoked by electrical stimulation of the vagus nerves in the presence of atropine, We have used novel, highly s elective tachykinin receptor antagonists, together with a procedure fo r on-line, breath-by-breath analysis of total lung resistance (R(L), s ubtractor method) and dynamic lung compliance (C-dyn), to investigate the role of tachykinins in this response in anaesthetized, paralysed g uinea-pigs, 2, In the presence of 1 mg/kg phosphoramidon (a neutral en dopeptidase inhibitor), CP 96345 (the non-peptide NK1 selective antago nist) at 200 nmol/kg had no effect on the increase in R(L) caused by v agal stimulation, but significantly inhibited the associated decrease in C-dyn. 3, The NK2 selective antagonist, MDL 29913 (1 mu mol/kg), si gnificantly antagonized the changes in both R(L) and C-dyn. In the abs ence of phosphoramidon, MDL 29913 again significantly inhibited the ch anges 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), al so effectively inhibited the responses to vagal stimulation and was mo re potent than MDL 29913, 5, These results emphasize the importance of the NK2 receptor system in mediating non-cholinergic bronchoconstrict ion evoked by vagal stimulation in the guinea-pig.