The effects of toluene diisocyanate and of capsaicin on human bronchial smooth muscle in vitro

Abstract

Toluene diisocyanate contracts guinea-pig bronchial smooth muscle through a mechanism involving capsaicin-sensitive sensory nerves. In the present study, we investigated the effects of toluene diisocyanate, capsaicin and tachykinins on isolated human bronchi. In 44 rings, toluene diisocyanate (0.3 mM) produced a relaxation which averaged 16.9 ± 1.1%, in ten rings it produced a shortening that was 15.1 ± 3.3% and in ten preparations it gave no response. A second administration of toluene diisocyanate (0.3 mM) always produced a relaxation (n = 13, 18.1 ± 3.9%). Capsaicin (0.03 mM) produced shortening in 15 (35± 6.6%) and relaxation in 11 preparations (41 ± 6.8%), whereas a second administration caused shortening in nine (25.1 ± 6.1%) and relaxation in 16 rings (36.4 ± 4.9%). When toluene diisocyanate was given after two consecutive capsaicin administrations, we observed shortening in two rings (10.0 ± 3.6%), relaxation in ten rings (15.9 ± 3.6%), and no response in four preparations. To test the role of NK 1 and NK 2 receptors in these conflicting responses, we performed concentration-response curves to different tachykinins. Substance P, neurokinin A and neurokinin A-(4–10), a specific NK 2 receptor agonist, gave a concentration-dependent shortening, with neurokinin A being the most effective and neurokinin A-(4–10) the least. The specific NK 1 receptor agonist, [Sar 9,Met(O 2) 11]substance P, produced both shortening and relaxation. We conclude that toluene diisocyanate and capsaicin may produce both shortening and relaxation in isolated human bronchi through NK 1 receptors.