Role of tachykinins in distilled water-induced bronchoconstriction in guinea-pigs.
BACKGROUND
An inhalation of ultrasonically nebulized distilled water (UNDW) induces bronchoconstriction only in asthmatics, but the mechanism underlying the response is not fully understood. We recently showed that bronchoconstriction occurs immediately after UNDW is inhaled 20min after an aerosolized antigen challenge in passively sensitized guinea-pigs.


OBJECTIVE
This study was conducted to examine the role of tachykinins in this response.


METHODS
Passively sensitized animals were anaesthetized and artificially ventilated, and changes in pressure at the airway opening (Pao) were measured as an overall index of airway narrowing. A tachykinin NK1 and NK2 dual receptor antagonist, FK224, and a tachykinin NK1 selective antagonist, FK888, were intravenously administered 15 min after the antigen challenge. The effects of capsaicin desensitization and a neutral endopeptidase inhibitor, phosphoramidon, were also examined.


RESULTS
FK224 and FK888 significantly (P < 0.05 and P < 0.05, respectively) reduced the time course curve of the increase in Pao caused by UNDW inhalation in a dose-dependent manner. The percentage increase in Pao from the preantigen challenge value at 1 min after the UNDW inhalation was 267.4+/-17.1, 358.0+/-33.7 and 412.4+/-27.6% with 10 mg/kg of FK224, 1.0 mg/kg of FK224 and vehicle, respectively, (P<0.01 between 10 mg/kg of FK224 and vehicle) and the value was 254.4+/-48.5% with 10 mg/kg of FK888, 327.1+/-57.6% with 1.0 mg/kg of FK888 and 418.5+/-39.0% with vehicle, respectively (P < 0.05 between 10 mg/kg of FK888 and vehicle). The capsaicin desensitization, but not phosphoramidon, significantly reduced the UNDW-induced increase in Pao.


CONCLUSIONS
These results suggest that tachykinins, at least substance P, are involved in a part of the UNDW-induced bronchoconstriction in our guinea-pig model.
The Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
M
M
Fujimura
T
T
Amemiya
S
S
Myou
M
M
Mizuguchi
Y
Y
Ishiura
S
S
Sasaki
T
T
Matsuda
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D002211:Capsaicin / Q000008:administration & dosage; D004151:Dipeptides / Q000494:pharmacology; D004195:Disease Models, Animal; D006020:Glycopeptides / Q000187:drug effects; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D009330:Nebulizers and Vaporizers; D010047:Ovalbumin / Q000008:administration & dosage; D010456:Peptides, Cyclic / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects; D015320:Tachykinins / Q000494:pharmacology*; D014867:Water / Q000008:administration & dosage*
D004151:Dipeptides; D006020:Glycopeptides; D007211:Indoles; D010456:Peptides, Cyclic; D015320:Tachykinins; D014867:Water; C075570:FK 224; C078949:FK 888; D010047:Ovalbumin; D002211:Capsaicin; C008890:phosphoramidon