THE EFFECTS OF TOLUENE DIISOCYANATE AND OF CAPSAICIN ON HUMAN BRONCHIAL SMOOTH-MUSCLE IN-VITRO

Toluene diisocyanate contracts guinea-pig bronchial smooth muscle thro ugh a mechanism involving capsaicin-sensitive sensory nerves. In the p resent study, we investigated the effects of toluene diisocyanate, cap saicin 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 to luene 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 ad ministration 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%), an d no response in four preparations. To test the role of NK1 and NK2 re ceptors in these conflicting responses, we performed concentration-res ponse curves to different tachykinins. Substance P, neurokinin A and n eurokinin A-(4-10), a specific NK2 receptor agonist, gave a concentrat ion-dependent shortening, with neurokinin A being the most effective a nd neurokinin A(4-10) the least. The specific NK1 receptor agonist, [S ar(9),Met(O-2)(11)]substance P, produced both shortening and relaxatio n. We conclude that toluene diisocyanate and capsaicin may produce bot h shortening and relaxation in isolated human bronchi through NK1 rece ptors.