The effects of toluene diisocyanate and of capsaicin on human bronchial smooth muscle in vitro.
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 NK1 and NK2 receptors in these conflicting responses, we performed concentration-response curves to different tachykinins. Substance P, neurokinin A and neurokinin A-(4-10), a specific NK2 receptor agonist, gave a concentration-dependent shortening, with neurokinin A being the most effective and neurokinin A-(4-10) the least. The specific NK1 receptor agonist, [Sar9, Met(O2)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 NK1 receptors.
Chitano
P
P
Institute of Occupational Medicine, University of Padua, Italy.
Di Blasi
P
P
Lucchini
R E
RE
Calabrò
F
F
Saetta
M
M
Maestrelli
P
P
Fabbri
L M
LM
Mapp
C E
CE
D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D001980:Bronchi / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007551:Isotonic Contraction / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D064729:Neurokinin-1 Receptor Antagonists; D010803:Physalaemin / Q000031:analogs & derivatives / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000187:drug effects; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000187:drug effects; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D014051:Toluene 2,4-Diisocyanate / Q000494:pharmacology*
D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C062618:substance P, Sar(9)-Met(O2)(11)-; C079014:GR 82334; D014051:Toluene 2,4-Diisocyanate; D010803:Physalaemin; D013373:Substance P; D007545:Isoproterenol; D000109:Acetylcholine; D002211:Capsaicin