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TACHYKININ RECEPTORS AND NON‐CHOLINERGIC BRONCHOCONSTRICTION IN THE ANAESTHETIZED GUINEA‐PIG
Author(s) -
Yuan Liqun,
Burcher Elizabeth,
Nail Bruce
Publication year - 1996
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1996.tb02582.x
Subject(s) - bronchoconstriction , phosphoramidon , tachykinin receptor , cholinergic , stimulation , chemistry , substance p , antagonist , endocrinology , medicine , neurokinin a , receptor antagonist , guinea pig , receptor , pharmacology , neuropeptide , biology , endothelin receptor , asthma
SUMMARY 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 NK 1 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 NK 2 selective antagonist, MDL 29913 (1 μmol/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 NK 2 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 NK 2 receptor system in mediating non‐cholinergic bronchoconstriction evoked by vagal stimulation in the guinea‐pig.